Skip to main content

Modeling Hereditary Spastic Paraplegias in Fruit Flies: Potential of Its Genetic Paraphernalia

  • Chapter
  • First Online:
Insights into Human Neurodegeneration: Lessons Learnt from Drosophila

Abstract

Hereditary spastic paraplegias (HSPs) are a large group of heterogeneous inherited neurological diseases characterized by spasticity or progressive stiffness in the lower extremities. The genetic basis of HSPs is very diverse, and the number of candidate genes being identified has been increasing due to better diagnostic approaches, including the advance and access of next-generation sequencing. Currently, the number of genomic loci associated with HSPs in humans are more than 80 and the corresponding number of identifiable genes are greater than 70. Drosophila has evolved as a powerful genetic model to explore these disease-causing genes in vivo. A comprehensive review of the previously studied HSP causative genes in flies revealed high similarity and potential of these organisms to provide novel insights into the underlying cellular pathways. We also found high conservation of HSP-related genes in flies with more than 60% of the human genes having corresponding sequences in Drosophila. Therefore, the study of HSP genes in flies can unravel valuable information for designing future therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abel, A., Fonknechten, N., Hofer, A., Dürr, A., Cruaud, C., Voit, T., Weissenbach, J., Brice, A., Klimpe, S., Auburger, G., et al. (2004). Early onset autosomal dominant spastic paraplegia caused by novel mutations in SPG3A. Neurogenetics, 5, 239–243.

    Article  CAS  PubMed  Google Scholar 

  • Aberle, H., Haghighi, A. P., Fetter, R. D., McCabe, B. D., Magalhães, T. R., & Goodman, C. S. (2002). Wishful thinking encodes a BMP type II receptor that regulates synaptic growth in Drosophila. Neuron, 33, 545–558.

    Article  CAS  PubMed  Google Scholar 

  • Albin, R. L., Koeppe, R. A., Rainier, S., & Fink, J. K. (2008). Normal dopaminergic nigrostriatal innervation in SPG3A hereditary spastic paraplegia. Journal of Neurogenetics, 22, 289–294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atkins, J., & Glynn, P. (2000). Membrane association of and critical residues in the catalytic domain of human neuropathy target esterase. The Journal of Biological Chemistry, 275, 24477–24483.

    Article  CAS  PubMed  Google Scholar 

  • Baas, P. W., Nadar, C. V., & Myers, K. A. (2006). Axonal transport of microtubules: The long and short of it. Traffic, 7, 490–498.

    Article  CAS  PubMed  Google Scholar 

  • Bakowska, J. C., Jenkins, R., Pendleton, J., & Blackstone, C. (2005). The Troyer syndrome (SPG20) protein spartin interacts with Eps15. Biochemical and Biophysical Research Communications, 334, 1042–1048.

    Article  CAS  PubMed  Google Scholar 

  • Bakowska, J. C., Jupille, H., Fatheddin, P., Puertollano, R., & Blackstone, C. (2007). Troyer syndrome protein spartin is mono-ubiquitinated and functions in EGF receptor trafficking. Molecular Biology of the Cell, 18, 1683–1692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barkus, R. V., Klyachko, O., Horiuchi, D., Dickson, B. J., Saxton, W. M., & Linstedt, A. (2007). Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides. MBoC, 19, 274–283.

    Article  PubMed  Google Scholar 

  • Baxter, S. L., Allard, D. E., Crowl, C., & Sherwood, N. T. (2014). Cold temperature improves mobility and survival in drosophila models of Autosomal-Dominant Hereditary Spastic Paraplegia (AD-HSP). Disease Models & Mechanisms. https://doi.org/10.1242/dmm.013987.

  • Bettencourt da Cruz, A., Wentzell, J., & Kretzschmar, D. (2008). Swiss cheese, a protein involved in progressive neurodegeneration, acts as a noncanonical regulatory subunit for PKA-C3. The Journal of Neuroscience, 28, 10885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bi, J., Wang, W., Liu, Z., Huang, X., Jiang, Q., Liu, G., Wang, Y., & Huang, X. (2014). Seipin promotes adipose tissue fat storage through the ER Ca2+-ATPase SERCA. Cell Metabolism, 19, 861–871.

    Article  CAS  PubMed  Google Scholar 

  • Bianchine, J. W., & Lewis, R. C. (1974). The MASA syndrome: A new heritable mental retardation syndrome. Clinical Genetics, 5, 298–306.

    Article  CAS  PubMed  Google Scholar 

  • Bier, E. (2005). Drosophila, the golden bug, emerges as a tool for human genetics. Nature Reviews Genetics, 6, 9–23.

    Article  CAS  PubMed  Google Scholar 

  • Blackstone, C. (2012). Cellular pathways of hereditary spastic paraplegia. Annual Review of Neuroscience, 35, 25–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blackstone, C. (2018). Chapter 41 – Hereditary spastic paraplegia. In D. H. Geschwind, H. L. Paulson, & C. Klein (Eds.), Handbook of clinical neurology (pp. 633–652). Amsterdam: Elsevier.

    Google Scholar 

  • Blackstone, C., O’Kane, C. J., & Reid, E. (2011). Hereditary spastic paraplegias: Membrane traffic and the motor pathway. Nature Reviews Neuroscience, 12, 31–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brand, A. H., & Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development, 118, 401–415.

    CAS  PubMed  Google Scholar 

  • Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., et al. (1998). Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell, 93, 973–983.

    Article  CAS  PubMed  Google Scholar 

  • Ciccarelli, F. D., Proukakis, C., Patel, H., Cross, H., Azam, S., Patton, M. A., Bork, P., & Crosby, A. H. (2003). The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. Genomics, 81, 437–441.

    Article  CAS  PubMed  Google Scholar 

  • Citterio, A., Arnoldi, A., Panzeri, E., Merlini, L., D’Angelo, M. G., Musumeci, O., Toscano, A., Bondi, A., Martinuzzi, A., Bresolin, N., et al. (2015). Variants in KIF1A gene in dominant and sporadic forms of hereditary spastic paraparesis. Journal of Neurology, 262, 2684–2690.

    Article  CAS  PubMed  Google Scholar 

  • Claudiani, P., Riano, E., Errico, A., Andolfi, G., & Rugarli, E. I. (2005). Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. Experimental Cell Research, 309, 358–369.

    Article  CAS  PubMed  Google Scholar 

  • Cross, H. E., & McKusick, V. A. (1967). The Troyer Syndrome: A recessive form of spastic paraplegia with distal muscle wasting. Archives of Neurology, 16, 473–485.

    Article  CAS  PubMed  Google Scholar 

  • Deik, A., Johannes, B., Rucker, J. C., Sánchez, E., Brodie, S. E., Deegan, E., Landy, K., Kajiwara, Y., Scelsa, S., Saunders-Pullman, R., et al. (2014). Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia. Journal of Neurology, 261, 2411–2423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Depienne, C., Fedirko, E., Forlani, S., Cazeneuve, C., Ribaï, P., Feki, I., Tallaksen, C., Nguyen, K., Stankoff, B., Ruberg, M., et al. (2007). Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia. Journal of Medical Genetics, 44, 281–284.

    Article  CAS  PubMed  Google Scholar 

  • Dor, T., Cinnamon, Y., Raymond, L., Shaag, A., Bouslam, N., Bouhouche, A., Gaussen, M., Meyer, V., Durr, A., Brice, A., et al. (2014). KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. Journal of Medical Genetics, 51, 137–142.

    Article  PubMed  Google Scholar 

  • Du, F., Ozdowski, E. F., Kotowski, I. K., Marchuk, D. A., & Sherwood, N. T. (2010). Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia. Human Molecular Genetics, 19, 1883–1896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duffy, J. B. (2002). GAL4 system in drosophila: A fly geneticist’s swiss army knife. Genesis, 34, 1–15.

    Article  CAS  PubMed  Google Scholar 

  • Dürr, A., Camuzat, A., Colin, E., Tallaksen, C., Hannequin, D., Coutinho, P., Fontaine, B., Rossi, A., Gil, R., Rousselle, C., et al. (2004). Atlastin1 mutations are frequent in young-onset autosomal dominant spastic paraplegia. Archives of Neurology, 61, 1867–1872.

    Article  PubMed  Google Scholar 

  • Dutta, S., Rieche, F., Eckl, N., Duch, C., & Kretzschmar, D. (2016). Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function. Disease Models & Mechanisms, 9, 283–294.

    Article  CAS  Google Scholar 

  • Ebbing, B., Mann, K., Starosta, A., Jaud, J., Schöls, L., Schüle, R., & Woehlke, G. (2008). Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Human Molecular Genetics, 17, 1245–1252.

    Article  CAS  PubMed  Google Scholar 

  • English, A. R., Zurek, N., & Voeltz, G. K. (2009). Peripheral ER structure and function. Current Opinion in Cell Biology, 21, 596–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erlich, Y., Edvardson, S., Hodges, E., Zenvirt, S., Thekkat, P., Shaag, A., Dor, T., Hannon, G. J., & Elpeleg, O. (2011). Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Research, 21, 658–664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Esteves, T., Durr, A., Mundwiller, E., Loureiro, J. L., Boutry, M., Gonzalez, M. A., Gauthier, J., El-Hachimi, K. H., Depienne, C., Muriel, M.-P., et al. (2014). Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. The American Journal of Human Genetics, 94, 268–277.

    Article  CAS  PubMed  Google Scholar 

  • Faber, I., Pereira, E. R., Martinez, A. R. M., França, M., & Teive, H. A. G. (2017). Hereditary spastic paraplegia from 1880 to 2017: An historical review. Arquivos de Neuro-Psiquiatria, 75, 813–818.

    Article  PubMed  Google Scholar 

  • Fink, J. K. (2013). Hereditary spastic paraplegia: Clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathologica, 126, 307–328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finsterer, J., Löscher, W., Quasthoff, S., Wanschitz, J., Auer-Grumbach, M., & Stevanin, G. (2012). Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. Journal of the Neurological Sciences, 318, 1–18.

    Article  PubMed  Google Scholar 

  • Fonknechten, N., Mavel, D., Byrne, P., Davoine, C.-S., Cruaud, C., Boentsch, D., Samson, D., Coutinho, P., Hutchinson, M., Monagle, P. M., et al. (2000). Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. Human Molecular Genetics, 9, 637–644.

    Article  CAS  PubMed  Google Scholar 

  • Fortini, M. E., Skupski, M. P., Boguski, M. S., & Hariharan, I. K. (2000). A survey of human disease gene counterparts in the drosophila genome. The Journal of Cell Biology, 150, F23–F30.

    Article  CAS  PubMed  Google Scholar 

  • Fransen, E., Lemmon, V., Van Camp, G., Vits, L., Coucke, P., & Willems, P. J. (1995). CRASH syndrome: Clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. European Journal of Human Genetics, 3, 273–284.

    Article  CAS  PubMed  Google Scholar 

  • Füger, P., Sreekumar, V., Schüle, R., Kern, J. V., Stanchev, D. T., Schneider, C. D., Karle, K. N., Daub, K. J., Siegert, V. K., Flötenmeyer, M., et al. (2012). Spastic paraplegia mutation N256S in the neuronal microtubule motor KIF5A disrupts axonal transport in a drosophila HSP model. PLoS Genetics, 8(11), e1003066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gho, M., McDonald, K., Ganetzky, B., & Saxton, W. M. (1992). Effects of kinesin mutations on neuronal functions. Science, 258, 313–316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glynn, P. (2005). Neuropathy target esterase and phospholipid deacylation. Biochimica et Biophysica Acta, 1736, 87–93.

    Article  CAS  PubMed  Google Scholar 

  • Godenschwege, T. A., Kristiansen, L. V., Uthaman, S. B., Hortsch, M., & Murphey, R. K. (2006). A conserved role for Drosophila Neuroglian and human L1-CAM in central-synapse formation. Current Biology, 16, 12–23.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein, L. S. B. (2001). Kinesin molecular motors: Transport pathways, receptors, and human disease. PNAS, 98, 6999–7003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstein, L. S. B., & Yang, Z. (2000). Microtubule-based transport systems in neurons: The roles of kinesins and dyneins. Annual Review of Neuroscience, 23, 39–71.

    Article  CAS  PubMed  Google Scholar 

  • González, C., & Couve, A. (2014). The axonal endoplasmic reticulum and protein trafficking: Cellular bootlegging south of the soma. Seminars in Cell & Developmental Biology, 27, 23–31.

    Article  CAS  Google Scholar 

  • Gregorio, C. D., Delgado, R., Ibacache, A., Sierralta, J., & Couve, A. (2017). Drosophila Atlastin in motor neurons is required for locomotion and presynaptic function. Journal of Cell Science. https://doi.org/10.1242/jcs.201657.

  • Hall, S. G., & Bieber, A. J. (1997). Mutations in the Drosophila Neuroglian cell adhesion molecule affect motor neuron pathfinding and peripheral nervous system patterning. Developmental Neurobiology, 32, 325–340.

    Article  CAS  Google Scholar 

  • Harding, A. E. (1983). Classification of the hereditary ataxias and paraplegias. The Lancet, 321, 1151–1155.

    Article  Google Scholar 

  • Harding, A. E. (1993). Hereditary spastic paraplegias. Seminars in Neurology, 13, 333–336.

    Article  CAS  PubMed  Google Scholar 

  • Hazan, J., Fonknechten, N., Mavel, D., Paternotte, C., Samson, D., Artiguenave, F., Davoine, C.-S., Cruaud, C., Dürr, A., Wincker, P., et al. (1999). Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nature Genetics, 23, 296–303.

    Article  CAS  PubMed  Google Scholar 

  • Heisenberg, M., & Bohl, K. (1979). Isolation of anatomical brain mutants of Drosophila by histological means. Zeitschrift Fur Naturforschung. Section C. Biosciences, 34, 143–147.

    Article  Google Scholar 

  • Henthorn, K. S., Roux, M. S., Herrera, C., Goldstein, L. S. B., & Zhu, X. (2011). A role for kinesin heavy chain in controlling vesicle transport into dendrites in Drosophila. MBoC, 22, 4038–4046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirokawa, N. (1998). Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science, 279, 519–526.

    Article  CAS  PubMed  Google Scholar 

  • Hotchkiss, L., Donkervoort, S., Leach, M. E., Mohassel, P., Bharucha-Goebel, D. X., Bradley, N., Nguyen, D., Hu, Y., Gurgel-Giannetti, J., & Bönnemann, C. G. (2016). Novel De novo mutations in KIF1A as a cause of hereditary spastic paraplegia with progressive central nervous system involvement. Journal of Child Neurology, 31, 1114–1119.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu, J., Shibata, Y., Voss, C., Shemesh, T., Li, Z., Coughlin, M., Kozlov, M. M., Rapoport, T. A., & Prinz, W. A. (2008). Membrane proteins of the endoplasmic reticulum induce high-curvature tubules. Science, 319, 1247–1250.

    Article  CAS  PubMed  Google Scholar 

  • Hu, J., Shibata, Y., Zhu, P.-P., Voss, C., Rismanchi, N., Prinz, W. A., Rapoport, T. A., & Blackstone, C. (2009). A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell, 138, 549–561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurd, D. D., & Saxton, W. M. (1996). Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in drosophila. Genetics, 144, 1075–1085.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Inlow, J. K., & Restifo, L. L. (2004). Molecular and comparative genetics of mental retardation. Genetics, 166, 835–881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Islam, R., Kristiansen, L. V., Romani, S., Garcia-Alonso, L., & Hortsch, M. (2004). Activation of EGF receptor kinase by L1-mediated homophilic cell interactions. Molecular Biology of the Cell, 15, 2003–2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ito, D., Fujisawa, T., Iida, H., & Suzuki, N. (2008). Characterization of seipin/BSCL2, a protein associated with spastic paraplegia 17. Neurobiology of Disease, 31, 266–277.

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal, M., Sandoval, H., Zhang, K., Bayat, V., & Bellen, H. J. (2012). Probing mechanisms that underlie human neurodegenerative diseases in drosophila. Annual Review of Genetics, 46, 371–396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jinushi-Nakao, S., Arvind, R., Amikura, R., Kinameri, E., Liu, A. W., & Moore, A. W. (2007). Knot/collier and cut control different aspects of dendrite cytoskeleton and synergize to define final arbor shape. Neuron, 56, 963–978.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, M. K. (1990). Organophosphates and delayed neuropathy--Is NTE alive and well? Toxicology and Applied Pharmacology, 102, 385–399.

    Article  CAS  PubMed  Google Scholar 

  • Jouet, M., Rosenthal, A., Armstrong, G., MacFarlane, J., Stevenson, R., Paterson, J., Metzenberg, A., Ionasescu, V., Temple, K., & Kenwrick, S. (1994). X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nature Genetics, 7, 402–407.

    Article  CAS  PubMed  Google Scholar 

  • Kanai, Y., Okada, Y., Tanaka, Y., Harada, A., Terada, S., & Hirokawa, N. (2000). KIF5C, a novel neuronal Kinesin enriched in motor neurons. The Journal of Neuroscience, 20, 6374–6384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanai, Y., Dohmae, N., & Hirokawa, N. (2004). Kinesin transports RNA: Isolation and characterization of an RNA-transporting granule. Neuron, 43, 513–525.

    Article  CAS  PubMed  Google Scholar 

  • Kern, J. V., Zhang, Y. V., Kramer, S., Brenman, J. E., & Rasse, T. M. (2013). The Kinesin-3, Unc-104 regulates dendrite morphogenesis and synaptic development in drosophila. Genetics, 195, 59–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klebe, S., Deuschl, G., & Stolze, H. (2006). Methylphenidate fails to improve gait and muscle tone in patients with sporadic and hereditary spastic paraplegia. Movement Disorders, 21, 1468–1471.

    Article  PubMed  Google Scholar 

  • Klebe, S., Lossos, A., Azzedine, H., Mundwiller, E., Sheffer, R., Gaussen, M., Marelli, C., Nawara, M., Carpentier, W., Meyer, V., et al. (2012). KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: Distinct phenotypes according to the nature of the mutations. European Journal of Human Genetics, 20, 645–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klebe, S., Stevanin, G., & Depienne, C. (2015). Clinical and genetic heterogeneity in hereditary spastic paraplegias: From SPG1 to SPG72 and still counting. Revue Neurologique (Paris), 171, 505–530.

    Article  CAS  Google Scholar 

  • Kmoch, S., Majewski, J., Ramamurthy, V., Cao, S., Fahiminiya, S., Ren, H., MacDonald, I. M., Lopez, I., Sun, V., Keser, V., et al. (2015). Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness. Nature Communications, 6, 5614.

    Article  CAS  PubMed  Google Scholar 

  • Koh, T.-W., Korolchuk, V. I., Wairkar, Y. P., Jiao, W., Evergren, E., Pan, H., Zhou, Y., Venken, K. J. T., Shupliakov, O., Robinson, I. M., et al. (2007). Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. The Journal of Cell Biology, 178, 309–322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kozak, M. (2002). Pushing the limits of the scanning mechanism for initiation of translation. Gene, 299, 1–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kretzschmar, D., Hasan, G., Sharma, S., Heisenberg, M., & Benzer, S. (1997). The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila. The Journal of Neuroscience, 17, 7425–7432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, Y., Paik, D., Bang, S., Kang, J., Chun, B., Lee, S., Bae, E., Chung, J., & Kim, J. (2008). Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila. Neurobiology of Aging, 29, 84–94.

    Article  CAS  PubMed  Google Scholar 

  • Lee, M., Paik, S. K., Lee, M.-J., Kim, Y.-J., Kim, S., Nahm, M., Oh, S.-J., Kim, H.-M., Yim, J., Lee, C. J., et al. (2009). Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development. Developmental Biology, 330, 250–262.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J.-R., Srour, M., Kim, D., Hamdan, F. F., Lim, S.-H., Brunel-Guitton, C., Décarie, J.-C., Rossignol, E., Mitchell, G. A., Schreiber, A., et al. (2015). De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy. Human Mutation, 36, 69–78.

    Article  CAS  PubMed  Google Scholar 

  • Lotti, M. (1991). The pathogenesis of organophosphate polyneuropathy. Critical Reviews in Toxicology, 21, 465–487.

    Article  CAS  PubMed  Google Scholar 

  • Lu, B., & Vogel, H. (2009). Drosophila models of neurodegenerative diseases. Annual Review of Pathology: Mechanisms of Disease, 4, 315–342.

    Article  CAS  Google Scholar 

  • Lush, M. J., Li, Y., Read, D. J., Willis, A. C., & Glynn, P. (1998). Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. The Biochemical Journal, 332(Pt 1), 1–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lykke-Andersen, S., & Jensen, T. H. (2015). Nonsense-mediated mRNA decay: An intricate machinery that shapes transcriptomes. Nature Reviews Molecular Cell Biology, 16, 665–677.

    Article  CAS  PubMed  Google Scholar 

  • Manzini, M. C., Rajab, A., Maynard, T. M., Mochida, G. H., Tan, W.-H., Nasir, R., Hill, R. S., Gleason, D., Al Saffar, M., Partlow, J. N., et al. (2010). Developmental and degenerative features in a complicated spastic paraplegia. Annals of Neurology, 67, 516–525.

    Article  CAS  PubMed  Google Scholar 

  • Marqués, G., Bao, H., Haerry, T. E., Shimell, M. J., Duchek, P., Zhang, B., & O’Connor, M. B. (2002). The Drosophila BMP type II receptor Wishful Thinking regulates neuromuscular synapse morphology and function. Neuron, 33, 529–543.

    Article  PubMed  Google Scholar 

  • McCabe, B. D., Marqués, G., Haghighi, A. P., Fetter, R. D., Crotty, M. L., Haerry, T. E., Goodman, C. S., & O’Connor, M. B. (2003). The BMP homolog Gbb provides a retrograde signal that regulates synaptic growth at the Drosophila neuromuscular junction. Neuron, 39, 241–254.

    Article  CAS  PubMed  Google Scholar 

  • McCabe, B. D., Hom, S., Aberle, H., Fetter, R. D., Marques, G., Haerry, T. E., Wan, H., O’Connor, M. B., Goodman, C. S., & Haghighi, A. P. (2004). Highwire regulates presynaptic BMP signaling essential for synaptic growth. Neuron, 41, 891–905.

    Article  CAS  PubMed  Google Scholar 

  • McGurk, L., Berson, A., & Bonini, N. M. (2015). Drosophila as an in vivo model for human neurodegenerative disease. Genetics, 201, 377–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miki, H., Okada, Y., & Hirokawa, N. (2005). Analysis of the kinesin superfamily: Insights into structure and function. Trends in Cell Biology, 15, 467–476.

    Article  CAS  PubMed  Google Scholar 

  • Montenegro, G., Rebelo, A. P., Connell, J., Allison, R., Babalini, C., D’Aloia, M., Montieri, P., Schüle, R., Ishiura, H., Price, J., et al. (2012). Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. The Journal of Clinical Investigation, 122, 538–544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moretto, A. (2000). Promoters and promotion of axonopathies. Toxicology Letters, 112–113, 17–21.

    Article  PubMed  Google Scholar 

  • Moser, M., Stempfl, T., Li, Y., Glynn, P., Büttner, R., & Kretzschmar, D. (2000). Cloning and expression of the murine sws/NTE gene. Mechanisms of Development, 90, 279–282.

    Article  CAS  PubMed  Google Scholar 

  • Mühlig-Versen, M., da Cruz, A. B., Tschäpe, J.-A., Moser, M., Büttner, R., Athenstaedt, K., Glynn, P., & Kretzschmar, D. (2005). Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila. The Journal of Neuroscience, 25, 2865–2873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nahm, M., Lee, M.-J., Parkinson, W., Lee, M., Kim, H., Kim, Y.-J., Kim, S., Cho, Y. S., Min, B.-M., Bae, Y. C., et al. (2013). Spartin regulates synaptic growth and neuronal survival by inhibiting BMP-mediated microtubule stabilization. Neuron, 77, 680–695.

    Article  CAS  PubMed  Google Scholar 

  • Namekawa, M., Ribai, P., Nelson, I., Forlani, S., Fellmann, F., Goizet, C., Depienne, C., Stevanin, G., Ruberg, M., Dürr, A., et al. (2006). SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. Neurology, 66, 112.

    Article  CAS  PubMed  Google Scholar 

  • Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B. J., Nalls, M. A., Keagle, P., et al. (2018). Genome-wide analyses identify KIF5A as a novel ALS gene. Neuron, 97, 1268–1283.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Sullivan, N. C., Jahn, T. R., Reid, E., & O’Kane, C. J. (2012). Reticulon-like-1, the Drosophila orthologue of the Hereditary Spastic Paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons. Human Molecular Genetics, 21, 3356–3365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orso, G., Martinuzzi, A., Rossetto, M. G., Sartori, E., Feany, M., & Daga, A. (2005). Disease-related phenotypes in a Drosophila model of hereditary spastic paraplegia are ameliorated by treatment with vinblastine. The Journal of Clinical Investigation, 115, 3026–3034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orso, G., Pendin, D., Liu, S., Tosetto, J., Moss, T. J., Faust, J. E., Micaroni, M., Egorova, A., Martinuzzi, A., McNew, J. A., et al. (2009). Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin. Nature, 460, 978–983.

    Article  CAS  PubMed  Google Scholar 

  • Ozdowski, E. F., Gayle, S., Bao, H., Zhang, B., & Sherwood, N. T. (2011). Loss of Drosophila melanogaster p21-activated kinase 3 suppresses defects in synapse structure and function caused by spastin mutations. Genetics, 189, 123–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ozdowski, E. F., Baxter, S. L., & Sherwood, N. T. (2015). Chapter 73 – Drosophila models of hereditary spastic paraplegia. In M. S. LeDoux (Ed.), Movement disorders (2nd ed., pp. 1103–1122). Boston: Academic Press.

    Chapter  Google Scholar 

  • Pack-Chung, E., Kurshan, P. T., Dickman, D. K., & Schwarz, T. L. (2007). A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Nature Neuroscience, 10, 980.

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulos, C., Orso, G., Mancuso, G., Herholz, M., Gumeni, S., Tadepalle, N., Jüngst, C., Tzschichholz, A., Schauss, A., Höning, S., et al. (2015). Spastin binds to lipid droplets and affects lipid metabolism. PLoS Genetics, 11, e1005149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pareek, G., Thomas, R. E., & Pallanck, L. J. (2018). Loss of the Drosophila m-AAA mitochondrial protease paraplegin results in mitochondrial dysfunction, shortened lifespan, and neuronal and muscular degeneration. Cell Death & Disease, 9, 304.

    Article  CAS  Google Scholar 

  • Park, S. H., Zhu, P.-P., Parker, R. L., & Blackstone, C. (2010). Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. The Journal of Clinical Investigation, 120, 1097–1110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel, H., Hart, P. E., Warner, T. T., Houlston, R. S., Patton, M. A., Jeffery, S., & Crosby, A. H. (2001). The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype. American Journal of Human Genetics, 69, 209–215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel, H., Cross, H., Proukakis, C., Hershberger, R., Bork, P., Ciccarelli, F. D., Patton, M. A., McKusick, V. A., & Crosby, A. H. (2002). SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nature Genetics, 31, 347.

    Article  CAS  PubMed  Google Scholar 

  • Popp, M. W., & Maquat, L. E. (2016). Leveraging rules of nonsense-mediated mRNA decay for genome engineering and personalized medicine. Cell, 165, 1319–1322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Praefcke, G. J. K., & McMahon, H. T. (2004). The dynamin superfamily: Universal membrane tubulation and fission molecules? Nature Reviews Molecular Cell Biology, 5, 133–147.

    Article  CAS  PubMed  Google Scholar 

  • Proukakis, C., Cross, H., Patel, H., Patton, M. A., Valentine, A., & Crosby, A. H. (2004). Troyer syndrome revisited. Journal of Neurology, 251, 1105–1110.

    Article  PubMed  Google Scholar 

  • Rainier, S., Chai, J.-H., Tokarz, D., Nicholls, R. D., & Fink, J. K. (2003). NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). The American Journal of Human Genetics, 73, 967–971.

    Article  CAS  PubMed  Google Scholar 

  • Rainier, S., Bui, M., Mark, E., Thomas, D., Tokarz, D., Ming, L., Delaney, C., Richardson, R. J., Albers, J. W., Matsunami, N., et al. (2008). Neuropathy target esterase gene mutations cause motor neuron disease. American Journal of Human Genetics, 82, 780–785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rainier, S., Albers, J. W., Dyck, P. J., Eldevik, O. P., Wilcock, S., Richardson, R. J., & Fink, J. K. (2011). Motor neuron disease due to neuropathy target esterase gene mutation: Clinical features of the index families. Muscle & Nerve, 43, 19–25.

    Article  Google Scholar 

  • Rao, K., Stone, M. C., Weiner, A. T., Gheres, K. W., Zhou, C., Deitcher, D. L., Levitan, E. S., Rolls, M. M., & Forscher, P. (2016). Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration. MBoC, 27, 3245–3256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid, E. (2003). Science in motion: Common molecular pathological themes emerge in the hereditary spastic paraplegias. Journal of Medical Genetics, 40, 81–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid, E., Kloos, M., Ashley-Koch, A., Hughes, L., Bevan, S., Svenson, I. K., Graham, F. L., Gaskell, P. C., Dearlove, A., Pericak-Vance, M. A., et al. (2002). A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). The American Journal of Human Genetics, 71, 1189–1194.

    Article  CAS  PubMed  Google Scholar 

  • Reiter, L. T., Potocki, L., Chien, S., Gribskov, M., & Bier, E. (2001). A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Research, 11, 1114–1125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ring, J., Rockenfeller, P., Abraham, C., Tadic, J., Poglitsch, M., Schimmel, K., Westermayer, J., Schauer, S., Achleitner, B., Schimpel, C., et al. (2017). Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin. Microbial Cell, 4, 411–422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rismanchi, N., Soderblom, C., Stadler, J., Zhu, P.-P., & Blackstone, C. (2008). Atlastin GTPases are required for Golgi apparatus and ER morphogenesis. Human Molecular Genetics, 17, 1591–1604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roll-Mecak, A., & Vale, R. D. (2005). The Drosophila homologue of the hereditary spastic paraplegia protein, spastin, severs and disassembles microtubules. Current Biology, 15, 650–655.

    Article  CAS  PubMed  Google Scholar 

  • Röper, K. (2007). Rtnl1 is enriched in a specialized germline ER that associates with ribonucleoprotein granule components. Journal of Cell Science, 120, 1081–1092.

    Article  CAS  PubMed  Google Scholar 

  • Rosenthal, A., Jouet, M., & Kenwrick, S. (1992). Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nature Genetics, 2, 107–112.

    Article  CAS  PubMed  Google Scholar 

  • Ruano, L., Melo, C., Silva, M. C., & Coutinho, P. (2014). The global epidemiology of hereditary ataxia and spastic paraplegia: A systematic review of prevalence studies. NED, 42, 174–183.

    Google Scholar 

  • Rugarli, E. I., & Langer, T. (2006). Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia. Trends in Molecular Medicine, 12, 262–269.

    Article  CAS  PubMed  Google Scholar 

  • Saxton, W. M., Hicks, J., Goldstein, L. S. B., & Raff, E. C. (1991). Kinesin heavy chain is essential for viability and neuromuscular functions in drosophila, but mutants show no defects in mitosis. Cell, 64, 1093–1102.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt, I., Thomas, S., Kain, P., Risse, B., Naffin, E., & Klämbt, C. (2012). Kinesin heavy chain function in drosophila glial cells controls neuronal activity. The Journal of Neuroscience, 32, 7466–7476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sherwood, N. T., Sun, Q., Xue, M., Zhang, B., & Zinn, K. (2004). Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function. PLoS Biology, 2(12), e429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoukier, M., Neesen, J., Sauter, S. M., Argyriou, L., Doerwald, N., Pantakani, D. K., & Mannan, A. U. (2009). Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia. European Journal of Human Genetics, 17, 187–194.

    Article  CAS  PubMed  Google Scholar 

  • Smith, M. I. (1930). The pharmacological action of certain phenol esters, with special reference to the etiology of so-called ginger paralysis (second report). Public Health Reports (1896–1970), 45, 2509–2524.

    Article  CAS  Google Scholar 

  • Solowska, J. M., Morfini, G., Falnikar, A., Himes, B. T., Brady, S. T., Huang, D., & Baas, P. W. (2008). Quantitative and functional analyses of spastin in the nervous system: Implications for hereditary spastic paraplegia. The Journal of Neuroscience, 28, 2147–2157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solowska, J. M., Garbern, J. Y., & Baas, P. W. (2010). Evaluation of loss of function as an explanation for SPG4-based hereditary spastic paraplegia. Human Molecular Genetics, 19, 2767–2779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solowska, J. M., Rao, A. N., Baas, P. W., & Kaibuchi, K. (2017). Truncating mutations of SPAST associated with hereditary spastic paraplegia indicate greater accumulation and toxicity of the M1 isoform of spastin. MBoC, 28, 1728–1737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stone, M. C., Rao, K., Gheres, K. W., Kim, S., Tao, J., La Rochelle, C., Folker, C. T., Sherwood, N. T., & Rolls, M. M. (2012). Normal spastin gene dosage is specifically required for axon regeneration. Cell Reports, 2, 1340–1350.

    Article  CAS  PubMed  Google Scholar 

  • Summerville, J. B., Faust, J. F., Fan, E., Pendin, D., Daga, A., Formella, J., Stern, M., & McNew, J. A. (2016). The effects of ER morphology on synaptic structure and function in Drosophila melanogaster. Journal of Cell Science, 129, 1635–1648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Synofzik, M., Gonzalez, M. A., Lourenco, C. M., Coutelier, M., Haack, T. B., Rebelo, A., Hannequin, D., Strom, T. M., Prokisch, H., Kernstock, C., et al. (2014). PNPLA6 mutations cause Boucher-Neuhäuser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. Brain, 137, 69–77.

    Article  PubMed  Google Scholar 

  • Synofzik, M., Kernstock, C., Haack, T. B., & Schöls, L. (2015). Ataxia meets chorioretinal dystrophy and hypogonadism: Boucher-Neuhäuser syndrome due to PNPLA6 mutations. Journal of Neurology, Neurosurgery, and Psychiatry, 86, 580.

    Article  PubMed  Google Scholar 

  • Tesson, C., Koht, J., & Stevanin, G. (2015). Delving into the complexity of hereditary spastic paraplegias: How unexpected phenotypes and inheritance modes are revolutionizing their nosology. Human Genetics, 134, 511–538.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tian, Y., Bi, J., Shui, G., Liu, Z., Xiang, Y., Liu, Y., Wenk, M. R., Yang, H., & Huang, X. (2011). Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation. PLoS Genetics, 7, e1001364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Topaloglu, A. K., Lomniczi, A., Kretzschmar, D., Dissen, G. A., Kotan, L. D., McArdle, C. A., Koc, A. F., Hamel, B. C., Guclu, M., Papatya, E. D., et al. (2014). Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. The Journal of Clinical Endocrinology and Metabolism, 99, E2067–E2075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trotta, N., Orso, G., Rossetto, M. G., Daga, A., & Broadie, K. (2004). The hereditary spastic paraplegia gene, spastin, regulates microtubule stability to modulate synaptic structure and function. Current Biology, 14, 1135–1147.

    Article  CAS  PubMed  Google Scholar 

  • Tsang, H. T. H., Edwards, T. L., Wang, X., Connell, J. W., Davies, R. J., Durrington, H. J., O’Kane, C. J., Luzio, J. P., & Reid, E. (2009). The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling. Human Molecular Genetics, 18, 3805–3821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voeltz, G. K., Prinz, W. A., Shibata, Y., Rist, J. M., & Rapoport, T. A. (2006). A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell, 124, 573–586.

    Article  CAS  PubMed  Google Scholar 

  • Wakefield, S., & Tear, G. (2006). The Drosophila reticulon, Rtnl-1, has multiple differentially expressed isoforms that are associated with a sub-compartment of the endoplasmic reticulum. Cellular and Molecular Life Sciences, 63, 2027–2038.

    Article  CAS  PubMed  Google Scholar 

  • Wang, L., & Brown, A. (2010). A hereditary spastic paraplegia mutation in kinesin-1A/KIF5A disrupts neurofilament transport. Molecular Neurodegeneration, 5, 52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, X., & O’Kane, C. J. (2008). Hereditary spastic paraplegia genes in Drosophila: Dissecting their roles in axonal degeneration and intracellular traffic. SEB Experimental Biology Series, 60, 161–182.

    CAS  PubMed  Google Scholar 

  • Wang, X., Shaw, W. R., Tsang, H. T. H., Reid, E., & O’Kane, C. J. (2007). Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules. Nature Neuroscience, 10, 177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wentzell, J. S., Cassar, M., & Kretzschmar, D. (2014). Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese/NTE lead to behavioral deficits and neurodegeneration. PLoS One, 9, e87526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wharton, S. B., McDermott, C. J., Grierson, A. J., Wood, J. D., Gelsthorpe, C., Ince, P. G., & Shaw, P. J. (2003). The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin gene. Journal of Neuropathology and Experimental Neurology, 62, 1166–1177.

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson, P. A., Hart, P. E., Patel, H., Warner, T. T., & Crosby, A. H. (2003). SPG3A mutation screening in English families with early onset autosomal dominant hereditary spastic paraplegia. Journal of the Neurological Sciences, 216, 43–45.

    Article  CAS  PubMed  Google Scholar 

  • Windpassinger, C., Auer-Grumbach, M., Irobi, J., Patel, H., Petek, E., Hörl, G., Malli, R., Reed, J. A., Dierick, I., Verpoorten, N., et al. (2004). Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and silver syndrome. Nature Genetics, 36, 271–276.

    Article  CAS  PubMed  Google Scholar 

  • Wood, J. D., Landers, J. A., Bingley, M., McDermott, C. J., Thomas-McArthur, V., Gleadall, L. J., Shaw, P. J., & Cunliffe, V. T. (2006). The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo. Human Molecular Genetics, 15, 2763–2771.

    Article  CAS  PubMed  Google Scholar 

  • Xu, S., Stern, M., & McNew, J. A. (2016). Beneficial effects of rapamycin in a Drosophila model for hereditary spastic paraplegia. Journal of Cell Science. https://doi.org/10.1242/jcs.196741.

  • Yalçın, B., Zhao, L., Stofanko, M., O’Sullivan, N. C., Kang, Z. H., Roost, A., Thomas, M. R., Zaessinger, S., Blard, O., Patto, A. L., et al. (2017). Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins. eLife, 6, e23882.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yamamoto, M., Ueda, R., Takahashi, K., Saigo, K., & Uemura, T. (2006). Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuron-glia interface. Current Biology, 16, 1678–1683.

    Article  CAS  PubMed  Google Scholar 

  • Ylikallio, E., Kim, D., Isohanni, P., Auranen, M., Kim, E., Lönnqvist, T., & Tyynismaa, H. (2015). Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia. European Journal of Human Genetics, 23, 1427–1430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yonekawa, Y., Harada, A., Okada, Y., Funakoshi, T., Kanai, Y., Takei, Y., Terada, S., Noda, T., & Hirokawa, N. (1998). Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice. The Journal of Cell Biology, 141, 431–441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu, W., Qiang, L., Solowska, J. M., Karabay, A., Korulu, S., Baas, P. W., & Holzbaur, E. (2008). The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches. MBoC, 19, 1485–1498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaccheo, O., Dinsdale, D., Meacock, P. A., & Glynn, P. (2004). Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells. The Journal of Biological Chemistry, 279, 24024–24033.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y. V., Hannan, S. B., Stapper, Z. A., Kern, J. V., Jahn, T. R., & Rasse, T. M. (2016). The drosophila KIF1A homolog unc-104 is important for site-specific synapse maturation. Frontiers in Cellular Neuroscience, 10, 207.

    PubMed  PubMed Central  Google Scholar 

  • Zhang, Y. V., Hannan, S. B., Kern, J. V., Stanchev, D. T., Koç, B., Jahn, T. R., & Rasse, T. M. (2017). The KIF1A homolog Unc-104 is important for spontaneous release, postsynaptic density maturation and perisynaptic scaffold organization. Scientific Reports, 7, 38172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, X., Alvarado, D., Rainier, S., Lemons, R., Hedera, P., Weber, C. H., Tukel, T., Apak, M., Heiman-Patterson, T., Ming, L., et al. (2001). Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nature Genetics, 29, 326–331.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, P.-P., Patterson, A., Lavoie, B., Stadler, J., Shoeb, M., Patel, R., & Blackstone, C. (2003). Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin. The Journal of Biological Chemistry, 278, 49063–49071.

    Article  CAS  PubMed  Google Scholar 

  • Züchner, S., Wang, G., Tran-Viet, K.-N., Nance, M. A., Gaskell, P. C., Vance, J. M., Ashley-Koch, A. E., & Pericak-Vance, M. A. (2006). Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31. The American Journal of Human Genetics, 79, 365–369.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vimlesh Kumar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bhat, S.A., Kumar, V. (2019). Modeling Hereditary Spastic Paraplegias in Fruit Flies: Potential of Its Genetic Paraphernalia. In: Mutsuddi, M., Mukherjee, A. (eds) Insights into Human Neurodegeneration: Lessons Learnt from Drosophila. Springer, Singapore. https://doi.org/10.1007/978-981-13-2218-1_14

Download citation

Publish with us

Policies and ethics