Roles for beta pat-3 integrins in development and function of Caenorhabditis elegans muscles and gonads

Heterodimeric integrin receptors for extracellular matrix (ECM) play vital roles in bidirectional signaling during tissue development, organization, r emodeling, and repair. The beta integrin subunit cytoplasmic domain is esse ntial for transmission of many of these signals and overexpression of an im paired beta tail in cultured cells inhibits endogenous integrins. Unlike ve rtebrates, which have at least nine beta subunit genes, the nematode Caenor habditis elegans expresses only one beta subunit (beta pat-3), and a null m utation in this gene causes embryonic lethality. To determine the functions of integrins during larval development and in adult tissues, we have taken a dominant negative approach by expression of an HA-beta tail transgene co mposed of a hemagglutinin (RA) epitope tag extracellular domain connected t o the beta pat-3 transmembrane and cytoplasmic domains. Expression of this transgene in muscle and gonad, major sites of integrin expression, caused a variety of phenotypes dependent on the level of transgene expression. Abno rmalities in body wall and sex muscles led to uncoordinated movement and eg g-laying defects. Significant anomalies in migration and pathfinding were c aused by tissue-specific expression of HA-beta tail in the distal tip cells (DTC), the cells that direct gonad morphogenesis. A pat-3 gene with Tyr to Phe mutations in the cytoplasmic domain was able to rescue pat-3 null anim als but also showed DTC migration defects. These results show that beta pat -3 plays important roles in post-embryonic organogenesis and tissue functio n.