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Class Ix Myosins

Negative Regulators of the Small GTP-binding Protein Rho

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Myosins

Part of the book series: Proteins and Cell Regulation ((PROR,volume 7))

Abstract

Class IX myosins are found in animals from invertebrates to vertebrates. Invertebrates contain a single myosin IX gene, whereas vertebrates contain two myosin IX genes, MYO9A and MYO9B. Mammalian Myo9b, the only class IX myosin studied so far, has unique motor properties. It is the first myosin for which ATP hydrolysis is the rate-limiting step in the chemical cycle and although it is a single-headed myosin, it can take multiple steps along F-actin before dissociating. Class IX myosins are motorized signaling molecules that contain in their tail domain a Rho GTPase-activating protein (GAP) activity. Mammalian members of myosin class IX negatively regulate the monomeric GTP-binding proteins RhoA-C. In cells, Myo9b accumulates in regions of active actin polymerization such as in extending lamellipodia. In these regions Myo9b might locally down regulate contractility and adhesion that are controlled by Rho activity and thereby contribute to sustained lamellipodial extension and cell polarity.

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References

  • Amundsen, S. S., Monsuur, A. J., Wapenaar, M. C., Lie, B. A., Ek, J., Gudjónsdóttir, A. H., Ascher, H., Wijmenga, C., and Sollid, L. M. (2006a). Association analysis of MYO9B gene polymorphisms with celiac disease in a Swedisch/Norwegian cohort. Hum. Immunol 67, 341–345.

    Google Scholar 

  • Amundsen, S. S., Vatn, M. and the IBSEN study group, Wijmenga, C., Sollid, L. M., and Lie, B. A. (2006b). Association analysis of MYO9B gene polymorphisms and inflammatory bowel disease in a Norwegian cohort. Tissue Antigens J compilation 68, 249–252.

    Google Scholar 

  • Bähler, M. and Rhoads, A. (2002). Calmodulin signaling via the IQ-motif. FEBS Lett. 513:107–113.

    Article  PubMed  Google Scholar 

  • Basu, J., Betz, A., Brose, N., and Rosenmund, C. (2007). Munc13-1 C1 domain activation lowers the energy barrier for synaptic vesicle function. J Neurosci 27, 1200–1210.

    Article  PubMed  CAS  Google Scholar 

  • Bement, W. M., Hasson, T., Wirth, J. A., Cheney, R. E., and Mooseker, M. S. (1994) Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types. Proc Natl Acad Sci USA 91, 6549–53.

    Article  PubMed  CAS  Google Scholar 

  • Canagarajah, B., Coluccio Leskow, F., Yew Seng Hong, J., Mischak, H., Saidi, L. F., Kazanietz, M. G., and Hurley, J. H. (2004). Structural mechanism for lipid activation of the Rac-specific GAP, ß2 chimaerin. Cell 119, 407–418.

    Google Scholar 

  • Chieregatti, E. and Bähler, M. (1996). The myosin myr 5 is phosphorylated at multiple sites. Mol. Biol. Cell (Supplement) 7, 373a.

    Google Scholar 

  • Chieregatti, E., Gärtner, A., Stöffler, H.-E., and Bähler, M. (1998). Myr 7 is a novel myosin IX-RhoGAP expressed in rat brain. J Cell Sci 111, 3597–3608.

    PubMed  CAS  Google Scholar 

  • Cirillo, G., Di Domenico, M. R., Corsi, I., Gagliardo, T., Del Giudice, E. M., Perrone, L., and Tolone, C. (2007). Do MYO9B genetic variants predispose to coeliac disease? An association study in a cohort of South Italian children. Dig Liver Dis 39, 228–231.

    Article  PubMed  CAS  Google Scholar 

  • De La Cruz, E. M., Ostap, E. M. (2004). Relating biochemistry and function in the myosin superfamily. Curr Opin Cell Biol 16, 61–7.

    Google Scholar 

  • Diakonova, M., Bokoch, G., and Swanson, J. A. (2002). Dynamics of cytoskeletal proteins during Fc receptor-mediated phagocytosis in macrophages. Mol Biol Cell 13, 402–411.

    Article  PubMed  CAS  Google Scholar 

  • Dries, D. R., Gallegos, L. L., and Newton, A. C. (2007). A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production. J Biol Chem 282, 826–830.

    Article  PubMed  CAS  Google Scholar 

  • Giordano, M., Marano, C., Mellai, M., Limongelli, M. G., Bolognesi, E., Clerget-Darpoux, F., Momigliano-Richiardi, P. and Greco, L. (2006). A family based study does not confirm the association of MYO9B with celiac disease in the Italian population. Genes Immun 7, 606–608.

    Article  PubMed  CAS  Google Scholar 

  • Gorman, S. W., Haider, N. B., Grieshammer, U., Swiderski, R. E., Kim, E., Welch, J. W., Searby, C., Leng, S., Carmi, R., Sheffield, V. C., and Duhl, D. M. (1999). The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23. Genomics 59, 150–160.

    Article  PubMed  CAS  Google Scholar 

  • Graf, B., Bähler, M., Hilpelä, P., Böwe, C., and Adam, T. (2000). Functional role for the class IX myosin myr5 in epithelial cell infection by Shigella flexneri. Cell Microbiol 2, 601–616.

    Google Scholar 

  • Grewal, P. K., Jones, A-M., Maconochie, M., Lemmers, R. J. F., Frants, R. R., and Hewitt, J. E. (1999). Cloning of the murine myosin gene Myo9b and identification of alternative splicing. Gene 240, 389–398.

    Google Scholar 

  • Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., and Meyer, T. (2006). PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane. Science 314, 1458–1461.

    Google Scholar 

  • Houdusse, A., Gaucher, J-F., Krementsova, E., Mui, S., Trybus, K. M., and Cohen, C. (2006). Crystal structure of apo-calmodulin bound to the first two IQ-motifs of myosin V reveals essential recognition features. Proc Natl Acad Sci USA 103, 19326–19331.

    Article  PubMed  CAS  Google Scholar 

  • Hunt, K. A., Monsuur, A. J., McArdle, W., Kumar, P. J., Travis, S. P. L., Walters, J. R. F., Jewell, D. P., Strachan, D. P., Playford, R. J., Wijmenga, C., and van Heel, D. A. (2006). Lack of association of MYO9B genetic variants with coeliac disease in a British cohort. Gut, doi:10.1136/gut.2005.086769.

    Google Scholar 

  • Hurley, J. H., Newton, A. C., Parker, P. J., Blumberg, P. M., and Nishizuka, Y. (1997). Taxonomy and function of C1 protein kinase C homology domains. Protein Sci 6, 477–480.

    Article  PubMed  CAS  Google Scholar 

  • Inoue, A., Saito, J., Ikebe, R., and Ikebe, M. (2002). Myosin IXb is a single-headed minus-end-directed processive motor. Nat Cell Biol 4, 302–306.

    Article  PubMed  CAS  Google Scholar 

  • Jaffe, B. A. and Hall, A. (2005). Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21, 247–269.

    Article  PubMed  CAS  Google Scholar 

  • Kalhammer, G., Bähler, M., Schmitz, F., Jöckel, J., and Block, C. (1997). Ras-binding domains: predicting function versus folding. FEBS Lett 414, 599–602.

    Article  PubMed  CAS  Google Scholar 

  • Kambara, T. and Ikebe, M. (2006). A unique ATP hydrolysis mechanism of single-headed processive myosin, myosin IX. J Biol Chem 281, 4949–4957.

    Article  PubMed  CAS  Google Scholar 

  • Monsuur, A. J. et al. (2005). Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect. Nat. Genet. 37, 1341–1344.

    Article  PubMed  CAS  Google Scholar 

  • Morinaga, N., Moss, J., and Vaughan, M. (1997). Cloning and expression of a cDNA encoding a bovine brain brefeldin A-sensitive guanine nucleotide-exchange protein for ADP-ribosylation factor. Proc Natl Acad Sci USA 94, 12926–31.

    Article  PubMed  CAS  Google Scholar 

  • Müller, R. T., Honnert, U., Rienhard, J., and Bähler, M. (1997).The rat myosin myr 5 is a GTPase-activating protein for Rho in vivo: essential role of arginine 1695. Mol Biol Cell 8, 2039–2053.

    Google Scholar 

  • Nalavadi, V., Nyitray, M., Bertolini, C., Adamek, N., Geeves, M. A., and Báhler, M. (2005). Kinetic mechanism of myosin IXB and the contributions of two class IX-specific regions. J Biol Chem 280, 38957–38968.

    Google Scholar 

  • Nishikawa, M., Nishikawa, S., Inoue, A., Iwane, A. H., Yanagida, T., and Ikebe, M. (2006). A unique mechanism for the processive movement of single-headed myosin-IX. Biochem Biophys Res Commun 343, 1159–1164.

    Article  PubMed  CAS  Google Scholar 

  • Núnez, C., Márquez, A., Varadé, J., Martinez, A., Polanco, I., Maluenda, C., Fernández-Arquero, M., de la Concha, E. G., and Urcelay, E. (2006). No evidence of association of the MYO9B polymorphisms with celiac disease in the Spanish population. Tissue Antigens J compilation 68, 489–492.

    Google Scholar 

  • O’Connell, C. B., and Mooseker, M. S. (2003). Native myosin-IXb is a plus-, not a minus-end-directed motor. Nat Cell Biol 5, 171–172.

    Article  PubMed  CAS  Google Scholar 

  • Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., and Mann, M. (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635–648.

    Article  PubMed  CAS  Google Scholar 

  • Ponting, C. P., and Benjamin, D. R. (1996). A novel family of Ras-binding domains. Trends Biochem Sci 21, 422–425.

    Article  PubMed  CAS  Google Scholar 

  • Post, P. L., Bokoch, G. M., and Mooseker, M. S. (1998) Human myosin-IXb is a mechanochemically active motor and a GAP for rho. J Cell Sci 111, 941–950.

    PubMed  CAS  Google Scholar 

  • Post, P. L., Tyska, M. J., O’Connell, C. B., Johung, K., Hayward, A., and Mooseker, M. S. (2002). Myosin-IXb is a single-headed and processive motor. J Biol Chem 277, 11679–11683.

    Article  PubMed  CAS  Google Scholar 

  • Reinhard, J. (1995). PhD thesis, Eberhard-Karls Universitát Túbingen, Germany.

    Google Scholar 

  • Reinhard, J., Scheel, A. A., Diekmann, D., Hall, A., Ruppert, C., and Báhler, M. (1995). A novel type of myosin implicated in signalling by rho family GTPases. EMBO J 14, 697–704.

    Google Scholar 

  • Ritt, D. A., Zhou, M., Conrads, T. P., Veenstra, D. P., Copeland, T. D., and Morrison, D. K. (2007). CK2 is a component of the KSR1 scaffold complex that contributes to Raf kinase activation. Curr Biol 17, 179–184.

    Article  PubMed  CAS  Google Scholar 

  • Saeki, N. Tokuo, H., and Ikebe, M. (2005). BIG1 is a binding partner of myosin IXb and regulates its Rho-GTPase activating protein activity. J Biol Chem 280, 10128–10134.

    Article  PubMed  CAS  Google Scholar 

  • Sapone, A., de Magistris, L., Pietzak, M. et al. (2006). Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55, 1443–1449.

    Article  PubMed  CAS  Google Scholar 

  • Shen, X., Hong, M-S., Moss, J., and Vaughan, M. (2007). BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein, is required for glycosylation and function of integrin. Proc Natl Acad Sci USA 104, 1230–1235.

    Article  PubMed  CAS  Google Scholar 

  • Van Bodegraven, A. A., Curley, C. R., Hunt, K. A., et al. (2006). Genetic variation in myosin IXB is associated with ulcerative colitis. Gastroenterology 131, 1768–1774.

    Google Scholar 

  • van den Boom, F., Düssmann, H., Uhlenbrock, K., Abouhamed, M., and Bähler, M. (2007). The myosin IXb motor activity targets the myosin IXb RhoGAP domain as cargo to sites of actin polymerization. Mol Biol Cell 18, 1507–1518.

    Google Scholar 

  • Wirth, J. A., Jensen, K. A., Post, P. L., Bement, W. M., and Mooseker, M. S. (1996). Human myosin-IXb, an unconventional myosin with a chimerin-like rho/rac GTPase-activating protein domain in its tail. J Cell Sci 109, 653–661.

    PubMed  CAS  Google Scholar 

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  1. Institut für Allgemeine Zoologie und Genetik, Westfälische-Wilhelms Universität, Schlossplatz 5, 48149 Mänster, Germany

    Martin BÄhler

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  1. Martin BÄhler
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BÄhler, M. (2008). Class Ix Myosins. In: Myosins. Proteins and Cell Regulation, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6519-4_13

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