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

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, Dracl, 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 Dracl proteins in these tissues. When expressed in neurons, Dracl 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.

Stress signaling in Drosophila

“…mbc mutant embryos are defective not only in myoblast fusion, but in DC and nervous system wiring (Erickson et al, 1997;Nolan et al, 1998). These phenotypes are reminiscent of those associated with overexpression of activated or antimorphic forms of Rac, and together with the genetic suppression data suggest involvement of Mbc in a common pathway with Rac (Erickson et al, 1997;Luo et al, 1994;Nolan et al, 1998). Mutations in mbc suppress both Rac-and Cdc42-, but not Rho-induced eye defects (Nolan et al, 1998).…”

FuRMAS: triggering myoblast fusion in Drosophila

“…Cdc42 seems not to play a major role in myoblast fusion (Schä fer et al, 2007) in contrast to Rac (see below). The first actin regulators that were identified to be important for myoblast fusion were the small rac-GTPases rac1, rac2 (Luo et al, 1994;Doberstein et al, 1997;Hakeda-Suzuki et al, 2002), and kette, the Drosophila homologue of Nap1/Hem-2 (Schröter et al, 2004). Interestingly, kette interacts genetically with the fcm-specifically expressed gene blow (Schröter et al, 2004).…”

“…However, myoblast fusion events are affected differently when overexpressing activated Rac. For example, in Drosophila, activated Rac blocks myoblast fusion (Luo et al, 1994;Doberstein et al, 1997), whereas in zebrafish, it leads to hyperfusion in fast-twitch muscles (Srinivas et al, 2007).…”

Visualizing new dimensions in Drosophila myoblast fusion

“…For example, mbc, Rac, kette and loner all have RNA expression in the early embryo that could be maternally loaded and could therefore affect the final phenotype. (41,47,51,57) Inefficient fusion could thus explain the differences in final nuclei number observed between kette, mbc, loner and Rac mutants and the intermediate fusion blocks often observed with rescue experiments. (21,49) rols, in contrast, is clearly not maternally loaded.…”