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Originally published as MBC in Press, 10.1091/mbc.E07-01-0047 on September 19, 2007

Vol. 18, Issue 12, 4721-4730, December 2007

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Dystroglycan and Protein O-Mannosyltransferases 1 and 2 Are Required to Maintain Integrity of Drosophila Larval Muscles

Nicola Haines, Sara Seabrooke, and Bryan A. Stewart

Department of Biology, University of Toronto, Mississauga, ON, Canada L5L 1C6

Submitted January 30, 2007; Accepted September 11, 2007
Monitoring Editor: Jeffrey Brodsky

In vertebrates, mutations in Protein O-mannosyltransferase1 (POMT1) or POMT2 are associated with muscular dystrophy due to a requirement for O-linked mannose glycans on the Dystroglycan (Dg) protein. In this study we examine larval body wall muscles of Drosophila mutant for Dg, or RNA interference knockdown for Dg and find defects in muscle attachment, altered muscle contraction, and a change in muscle membrane resistance. To determine if POMTs are required for Dg function in Drosophila, we examine larvae mutant for genes encoding POMT1 or POMT2. Larvae mutant for either POMT, or doubly mutant for both, show muscle attachment and muscle contraction phenotypes identical to those associated with reduced Dg function, consistent with a requirement for O-linked mannose on Drosophila Dg. Together these data establish a central role for Dg in maintaining integrity in Drosophila larval muscles and demonstrate the importance of glycosylation to Dg function in Drosophila. This study opens the possibility of using Drosophila to investigate muscular dystrophy.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-01-0047) on September 19, 2007.

Address correspondence to: Nicola Haines (nicola.haines{at}utoronto.ca).




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