Connections between integrins and Rac GTPase pathways control gonad formation and function in C-elegans

The integnins are a family of up heterodimeric transmembrane receptors that link extracellular matrix (ECM) proteins to the cytoskeleton and orchestrate cell behaviors. It's been suggested that integrins interact with Rho family small GTPases, such as Rho and Rac. We took advantage of a C. elegans nematode line expressing HA-beta tail, a beta integrin transgene inhibiting the functions of endogenous integrins, to determine the combined effects of reducing PAT-3 beta integrin and Rac pathway activities. Double mutants of HA-beta tail and unc-73, a guanine nucleotide exchange factor GEF for MIG-2/Rac, had body wall and vulval muscle abnormalities. On the other hand, HA-beta tail combined with mutant CED-5, another Rac interacting protein, showed ovulation defects and sterility. RNA-mediated interference (RNAi) of pat-3 on Rae mutant backgrounds also affected gonad structure and function. These results show a functional link between integrins and Rac signaling in muscles and gonads. Furthermore, data showing distinct phenotypes of HA-beta tail with unc-73 versus ced-5 suggest some tissue-specificity in the usage of Rae signaling pathways. (c) 2005 Elsevier B.V. All rights reserved.