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First published online November 26, 2007
doi: 10.1242/10.1242/dev.014027

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The transmembrane protein Perdido interacts with Grip and integrins to mediate myotube projection and attachment in the Drosophila embryo

Beatriz Estrada^1,2,*,, Stephen S. Gisselbrecht^1,* and Alan M. Michelson^1,3,

¹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
² Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Carretera de Utrera Km. 1, 41013 Sevilla, Spain.
³ National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Authors for correspondence (e-mails: bestmar{at}upo.es; michelsonam{at}nhlbi.nih.gov)

Accepted 21 September 2007

The molecular mechanisms underlying muscle guidance and formation of myotendinous junctions are poorly understood both in vertebrates and in Drosophila. We have identified a novel gene that is essential for Drosophila embryonic muscles to form proper projections and stable attachments to epidermal tendon cells. Loss-of-function of this gene - which we named perdido (perd)-results in rounded, unattached muscles. perd is expressed prior to myoblast fusion in a subset of muscle founder cells, and it encodes a conserved single-pass transmembrane cell adhesion protein that contains laminin globular extracellular domains and a small intracellular domain with a C-terminal PDZ-binding consensus sequence. Biochemical experiments revealed that the Perd intracellular domain interacts directly with one of the PDZ domains of the Glutamate receptor interacting protein (Grip), another factor required for formation of proper muscle projections. In addition, Perd is necessary to localize Grip to the plasma membrane of developing myofibers. Using a newly developed, whole-embryo RNA interference assay to analyze genetic interactions, perd was shown to interact not only with Grip but also with multiple edematous wings, which encodes one subunit of the PS1-βPS integrin expressed in tendon cells. These experiments uncovered a previously unrecognized role for the PS1-βPS integrin in the formation of muscle projections during early stages of myotendinous junction development. We propose that Perd regulates projection of myotube processes toward and subsequent differentiation of the myotendinous junction by priming formation of a protein complex through its intracellular interaction with Grip and its transient engagement with the tendon cell-expressed laminin-binding PS1-βPS integrin.

Key words: Muscle attachment, Myotendinous junction, Myogenesis, NG2, MCSP, Integrins, Drosophila

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				B. Estrada, S. S. Gisselbrecht, and A. M. Michelson The transmembrane protein Perdido interacts with Grip and integrins to mediate myotube projection and attachment in the Drosophila embryo J. Cell Sci., December 15, 2007; 120(24): e2407 - e2407. [Full Text]