This Article Full Text Full Text (PDF) Supplemental material Other Versions of this Article: MCB.00016-06v1 26/24/9442    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balagopalan, L. Articles by Abmayr, S. M. Search for Related Content PubMed PubMed Citation Articles by Balagopalan, L. Articles by Abmayr, S. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2006, p. 9442-9455, Vol. 26, No. 24
0270-7306/06/$08.00+0     doi:10.1128/MCB.00016-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The CDM Superfamily Protein MBC Directs Myoblast Fusion through a Mechanism That Requires Phosphatidylinositol 3,4,5-Triphosphate Binding but Is Independent of Direct Interaction with DCrk^,

Lakshmi Balagopalan ,^2,, Mei-Hui Chen,^1, Erika R. Geisbrecht,¹ and Susan M. Abmayr^1,2*

Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, Missouri 64110,¹ Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802²

Received 4 January 2006/ Returned for modification 9 February 2006/ Accepted 26 September 2006

myoblast city (mbc), a member of the CDM superfamily, is essential in the Drosophila melanogaster embryo for fusion of myoblasts into multinucleate fibers. Using germ line clones in which both maternal and zygotic contributions were eliminated and rescue of the zygotic loss-of-function phenotype, we established that mbc is required in the fusion-competent subset of myoblasts. Along with its close orthologs Dock180 and CED-5, MBC has an SH3 domain at its N terminus, conserved internal domains termed DHR1 and DHR2 (or "Docker"), and C-terminal proline-rich domains that associate with the adapter protein DCrk. The importance of these domains has been evaluated by the ability of MBC mutations and deletions to rescue the mbc loss-of-function muscle phenotype. We demonstrate that the SH3 and Docker domains are essential. Moreover, ethyl methanesulfonate-induced mutations that change amino acids within the MBC Docker domain to residues that are conserved in other CDM family members nevertheless eliminate MBC function in the embryo, which suggests that these sites may mediate interactions specific to Drosophila MBC. A functional requirement for the conserved DHR1 domain, which binds to phosphatidylinositol 3,4,5-triphosphate, implicates phosphoinositide signaling in myoblast fusion. Finally, the proline-rich C-terminal sites mediate strong interactions with DCrk, as expected. These sites are not required for MBC to rescue the muscle loss-of-function phenotype, however, which suggests that MBC's role in myoblast fusion can be carried out independently of direct DCrk binding.

Supplemental material for this article may be found at http://mcb.asm.org/.

Published ahead of print on 9 October 2006.

The first two authors contributed equally to this work.

Present address: LCMB, CCR, NCI, National Institutes of Health, Bethesda, MD 20892-4256.

This article has been cited by other articles:

• Hope, H., Bogliolo, S., Arkowitz, R. A., Bassilana, M. (2008). Activation of Rac1 by the Guanine Nucleotide Exchange Factor Dck1 Is Required for Invasive Filamentous Growth in the Pathogen Candida albicans. Mol. Biol. Cell 19: 3638-3651 [Abstract] [Full Text]  
• Kocherlakota, K. S., Wu, J.-m., McDermott, J., Abmayr, S. M. (2008). Analysis of the Cell Adhesion Molecule Sticks-and-Stones Reveals Multiple Redundant Functional Domains, Protein-Interaction Motifs and Phosphorylated Tyrosines That Direct Myoblast Fusion in Drosophila melanogaster. Genetics 178: 1371-1383 [Abstract] [Full Text]  
• Moore, C. A., Parkin, C. A., Bidet, Y., Ingham, P. W. (2007). A role for the Myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion. Development 134: 3145-3153 [Abstract] [Full Text]  
• Kinchen, J. M., Ravichandran, K. S. (2007). Journey to the grave: signaling events regulating removal of apoptotic cells. J. Cell Sci. 120: 2143-2149 [Abstract] [Full Text]