Skip to main content
Log in

Drosophila melanogaster gene Merlin interacts with the clathrin adaptor protein gene lap

  • General Genetics
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

The protein Merlin is involved in the regulation of cell proliferation and differentiation in the eyes and wings of Drosophila and is a homolog of the human protein encoded by the Neurofibromatosis 2 (NF2) gene whose mutations cause auricular nerve tumors. Recent studies show that Merlin and Expanded cooperatively regulate the recycling of membrane receptors, such as the epidermal growth factor receptor (EGFR). By performing a search for potential genetic interactions between Merlin (Mer) and the genes important for vesicular trafficking, we found that ectopic expression in the wing pouch of the clathrin adapter protein Lap involved in clathrin-mediated receptor endocytosis resulted in the formation of extra vein materials. On the one hand, coexpression of wild-type Merlin and lap in the wing pouch restored normal venation, while overexpression of a dominant-negative mutant Mer DBB together with lap enhanced ectopic vein formation. Using various constructs with Merlin truncated copies, we showed the C-terminal portion of the Merlin protein to be responsible for the Merlin-lap genetic interaction. Furthermore, we showed that the Merlin and Lap proteins colocalized at the cortex of the wing imaginal disc cells.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Held, L.I., Imaginal Discs: The Genetic and Cellular Logic of Pattern Formation, Cambridge: Cambridge Univ. Press, 2002.

    Book  Google Scholar 

  2. Blair, S.S., Wing Vein Patterning in Drosophila and the Analysis of Intercellular Signaling, Ann. Rev. Cell Dev. Biol., 2007, vol. 23, pp. 293–319.

    Article  CAS  Google Scholar 

  3. LaJeunesse, D.R., McCartney, B.M., and Fehon, R.G., Structural Analysis of Drosophila Merlin Reveals Functional Domains Important for Growth Control and Subcellular Localization, J. Cell Biol., 1998, vol. 141, pp. 1589–1599.

    Article  CAS  PubMed  Google Scholar 

  4. Maitra, S., Kulikauskas, R.M., Gavilan, H., and Fehon, R.G., The Tumor Suppressors Merlin and Expanded Function Cooperatively to Modulate Receptor Endocytosis and Signaling, Curr. Biol., 2006, vol. 16, pp. 702–709.

    Article  CAS  PubMed  Google Scholar 

  5. Rouleau, G.A., Merel, P., Luchtman, M., et al., Alteration in a New Gene Encoding a Putative Membrane-Organizing Protein Causes Neurofibromatosis Type 2, Nature, 1993, vol. 363, pp. 515–521.

    Article  CAS  PubMed  Google Scholar 

  6. Trofatter, J.A., MacCollin, M.M., Rutter, J.L., et al., A Novel Moesin-, Exrin-, Radixin-like Gene Is a Candidate for the Neurofibromatosis 2 Tumor-Suppressor, Cell, 1993, vol. 72, pp. 791–800.

    Article  CAS  PubMed  Google Scholar 

  7. Algrain, M., Arpin, M., and Louvard, D., Wizardry at the Cell Cortex, Curr. Biol., 1993, vol. 3, pp. 451–454.

    Article  CAS  PubMed  Google Scholar 

  8. Golovnina, K., Blinov, A., Akhmametyeva, E.M., et al., Evolution and Origin of Merlin, the Product of the Neurofibromatosis Type 2 (NF2) Tumor-Suppressor Gene, BMC Evol. Biol., 2005, vol. 5, pp. 69–86.

    Article  PubMed  Google Scholar 

  9. LaJeunesse, D.R., McCartney, B.M., and Fehon, R.G., A Systematic Screen for Dominant Second-Site Modifiers of Merlin/NF2 Phenotypes Reveals an Interaction with Blistered/DSRF and Scribbler, Genetics, 2001, vol. 158, pp. 667–679.

    CAS  PubMed  Google Scholar 

  10. Seto, E.S., Bellen, H.J., and Lloyd, T.E., When Cell Biology Meets Development: Endocytic Regulation of Signaling Pathways, Genes Dev., 2002, vol. 16, pp. 1314–1336.

    Article  CAS  PubMed  Google Scholar 

  11. Kirchhausen, T., Bonifacino, J.S., and Riezman, H., Linking Cargo to Vesicle Formation: Receptor Tail Interactions with Coat Proteins, Curr. Opin. Cell. Biol., 1997, vol. 9, pp. 488–495.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, B., Koh, Y.H., Beckstead, R.B., et al., Synaptic Vesicle Size and Number Are Regulated by a Clathrin Adaptor Protein Required for Endocytosis, Neuron, 1998, vol. 21, pp. 1465–1475.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang, B., Ganetzky, B., Bellen, H.J., and Murthy, V.N., Tailoring Uniform Coats for Synaptic Vesicles during Endocytosis, Neuron, 1999, vol. 23, pp. 419–422.

    Article  CAS  PubMed  Google Scholar 

  14. Wang, L.H., Sudhof, T.C., and Anderson, R.G., The Appendage Domain of Alpha-Adaptin Is a High Affinity Binding Site for Dynamin, J. Biol. Chem., 1995, vol. 270, pp. 10079–10083.

    Article  CAS  PubMed  Google Scholar 

  15. Ringstad, N., Nemoto, Y., and De Camilli, P., The SH3p4/Sh3p8/SH3p13 Protein Family: Binding Partners for Synaptojanin and Dynamin via a Grb2-Like Src Homology 3 Domain, Proc. Natl. Acad. Sci. USA, 1997, vol. 94, no. 15, pp. 8569–8574.

    Article  CAS  PubMed  Google Scholar 

  16. Newmyer, S.L. and Schmid, S.L., Dominant-Interfering Hsc70 Mutants Disrupt Multiple Stages of the Clathrin-Coated Vesicle Cycle in vivo, J. Cell Biol., 2001, vol. 152, pp. 607–620.

    Article  CAS  PubMed  Google Scholar 

  17. Griffiths, G. and Gruenberg, J., The Arguments for Preexisting Early and Late Endosomes, Trends Cell Biol., 1991, vol. 1, no. 1, pp. 5–9.

    Article  CAS  PubMed  Google Scholar 

  18. Murphy, R.F., Maturation Models for Endosome and Lysosome Biogenesis, Trends Cell Biol., 1991, vol. 1, pp. 77–82.

    Article  CAS  PubMed  Google Scholar 

  19. Seaman, M.N.J. and Luzio, J.P., Lysosomes and Other Late Compartments of the Endocytic Pathway, in Endocytosis: Frontiers in Molecular Biology, Oxford: Oxford Univ. Press, 2001, pp. 111–148.

    Google Scholar 

  20. Selva, E.M., Hong, K., Baeg, G.H., et al., Dual Role of the Fringe Connection Gene in Both Heparan Sulphate and Fringedependent Signalling Events, Nat. Cell Biol., 2001, vol. 3, pp. 809–815.

    Article  CAS  PubMed  Google Scholar 

  21. Entchev, E.V., Schwabedissen, A., and GonzalezGaitan, M., Gradient Formation of the TGF-Beta Homolog Dpp, Cell, 2000, vol. 103, pp. 981–991.

    Article  CAS  PubMed  Google Scholar 

  22. Tanaka, K., Kitagawa, Y., and Kadowaki, T., Drosophila Segment Polarity Gene Product Porcupine Stimulates the Posttranslational N-Glycosylation of Wingless in the Endoplasmic Reticulum, J. Biol. Chem., 2002, vol. 277, pp. 12816–12823.

    Article  CAS  PubMed  Google Scholar 

  23. Capdevila, J. and Guerrero, I., Targeted Expression of the Signaling Molecule Decapentaplegic Induces Pattern Duplications and Growth Alterations in Drosophila Wings, EMBO J., 1994, vol. 13, pp. 4459–4468.

    CAS  PubMed  Google Scholar 

  24. Coelho, C.M. and Leevers, S.J., Do Growth and Cell Division Rates Determine Cell Size in Multicellular Organisms?, J. Cell Sci., 2000, vol. 113, pp. 2927–2934.

    CAS  PubMed  Google Scholar 

  25. McCartney, B.M. and Fehon, R.G., Distinct Cellular and Subcellular Patterns of Expression Imply Distinct Functions for the Drosophila Homologues of Moesin and the Neurofibromatosis 2 Tumor Suppressor, merlin, J. Cell Biol., 1996, vol. 133, pp. 843–852.

    Article  CAS  PubMed  Google Scholar 

  26. Kirchhausen, T., Clathrin, Annu. Rev. Biochem., 2000, vol. 69, pp. 699–727.

    Article  CAS  PubMed  Google Scholar 

  27. Slepnev, V.I. and De Camilli, P., Accessory Factors in Clathrin-Dependent Synaptic Vesicle Endocytosis, Nat. Rev. Neurosci., 2000, vol. 1, pp. 161–172.

    Article  CAS  PubMed  Google Scholar 

  28. Lafer, E.M., Clathrin-Protein Interactions, Traffic, 2002, vol. 3, pp. 513–520.

    Article  CAS  PubMed  Google Scholar 

  29. Zhou, S., Sousa, R., Tannery, N.H., and Lafer, E.M., Characterization of a Novel Synapsespecific Protein: II. cDNA Cloning and Sequence Analysis of the F1-20 Protein, J. Neurosci., 1992, vol. 12, pp. 2144–2155.

    CAS  PubMed  Google Scholar 

  30. Schroder, S., Morris, S.A., Knorr, R., et al., Primary Structure of the Neuronal Clathrin-Associated Protein Auxilin and Its Expression in Bacteria, Eur. J. Biochem., 1995, vol. 228, pp. 297–304.

    Article  CAS  PubMed  Google Scholar 

  31. Curto, M., Cole, B.K., Lallemand, D., et al., ContactDependent Inhibition of EGFR Signaling by Nf2/Merlin, J. Cell Biol., 2007, vol. 177, pp. 893–903.

    Article  CAS  PubMed  Google Scholar 

  32. Gutmann, D.H., Sherman, L., Seftor, L., et al., Increased Expression of the NF2 Tumor Suppressor Gene Product, Merlin, Impairs Cell Motility, Adhesion and Spreading, Hum. Mol. Genet., 1999, vol. 8, pp. 267–275.

    Article  CAS  PubMed  Google Scholar 

  33. Zhai, L., Chaturvedi, D., and Cumberledge, S., Drosophila Wnt-1 Undergoes a Hydrophobic Modification and Is Targeted to Lipid Rafts, a Process That Requires Porcupine, J. Biol. Chem., 2004, vol. 279, pp. 33220–33227.

    Article  CAS  PubMed  Google Scholar 

  34. Nusse, R., Wnts and Hedgehogs: Lipid-Modified Proteins and Similarities in Signaling Mechanisms at the Cell Surface, Development, 2003, vol. 130, pp. 5297–5305.

    Article  CAS  PubMed  Google Scholar 

  35. Johnston, L.A. and Edgar, B.A., Wingless and Notch Regulate Cell-Cycle Arrest in the Developing Drosophila Wing, Nature, 1998, vol. 394, pp. 82–84.

    Article  CAS  PubMed  Google Scholar 

  36. Kopyl, S.A., Dorogova, N.V., Baimak, T.Yu., et al., Role of the porcupine Gene in the Development of the Wing Imaginal Disk of Drosophila melanogaster, Russ. J. Genet., 2008, vol. 44, no. 11, pp. 1290–1295.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. V. Omelyanchuk.

Additional information

Original Russian Text © S.A. Kopyl, N.V. Dorogova, E.M. Akhmametyeva, L.V. Omelyanchuk, L.-S. Chang, 2010, published in Genetika, 2010, Vol. 46, No. 3, pp. 314–320.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kopyl, S.A., Dorogova, N.V., Akhmametyeva, E.M. et al. Drosophila melanogaster gene Merlin interacts with the clathrin adaptor protein gene lap. Russ J Genet 46, 276–282 (2010). https://doi.org/10.1134/S1022795410030038

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795410030038

Keywords

Navigation