Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.

TLDR

Small GTPases of the Rac/Rho/Cdc42 subfamily are known to mediate actin cytoskeleton–membrane interactions in mammalian cells and yeast, but their in‑vivo roles in multicellular organisms remain unclear. The authors cloned Drosophila Drac1 and Dcdc42, which share 70 % sequence identity and are highly expressed in the nervous system and mesoderm, and expressed constitutively active and dominant‑negative variants in these tissues. Expression of mutant Drac1 in neurons produced axon outgrowth defects without affecting dendrites, while in muscle precursors it caused complete failure or abnormal myoblast fusion, and analogous Dcdc42 mutants produced distinct morphological defects, demonstrating unique morphogenetic functions for similar GTPases.

Abstract

The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in actin cytoskeleton-membrane interaction in mammalian cells and budding yeast. The in vivo functions of these GTPases in multicellular organisms are not known. We have cloned Drosophila homologs of rac and CDC42, Drac1, and Dcdc42. They share 70% amino acid sequence identity with each other, and both are highly expressed in the nervous system and mesoderm during neuronal and muscle differentiation, respectively. We expressed putative constitutively active and dominant-negative Drac1 proteins in these tissues. When expressed in neurons, Drac1 mutant proteins cause axon outgrowth defects in peripheral neurons without affecting dendrites. When expressed in muscle precursors, they cause complete failure of, or abnormality in, myoblast fusion. Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.