Heterodimeric integrin receptors for extracellular matrix (ECM) play vital roles in bidirectional signaling during tissue development, organization, remodeling, and repair. The β integrin subunit cytoplasmic domain is essential for transmission of many of these signals and overexpression of an unpaired β tail in cultured cells inhibits endogenous integrins. Unlike vertebrates, which have at least nine β subunit genes, the nematode Caenorhabditis elegans expresses only one β subunit (βpat-3), and a null mutation 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-βtail transgene composed of a hemagglutinin (HA) epitope tag extracellular domain connected to the βpat-3 transmembrane and cytoplasmic domains. Expression of this transgene in muscle and gonad, major sites of integrin expression, caused a variety of pheno-types dependent on the level of transgene expression. Abnormalities in body wall and sex muscles led to uncoordinated movement and egg-laying defects. Significant anomalies in migration and pathfinding were caused by tissue-specific expression of HA-βtail 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 animals but also showed DTC migration defects. These results show that βpat-3 plays important roles in post-embryonic organogenesis and tissue function.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology