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

By L. Luo, Y. Liao, L. Jan, Y. Jan. 1994

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.

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Citations in the corpus

• Genetic dissection of mutual interference between two consecutive learning tasks in Drosophila (2022, methodology): “The transgene dominantnegative Rac1 (Rac1DN) or constitutively active Rac1 (Rac1CA) was used to inhibit or increase Rac1 activity, respectively (Luo et al., 1994).”
• The role of the Rho GTPases in neuronal development. (2005, background): “The finding that constitutively active (CA) and dominant-negative (DN) mutants of the same Rho GTPase can cause aberrant phenotypes underscores the importance of tight regulation of Rho GTPase activity and the ability to cycle between an active GTP-bound form and an inactive GDPbound form for normal”
• Cdc42-Dependent Forgetting Regulates Repetition Effect in Prolonging Memory Retention. (2016, background): “To determine its role in forgetting, Cdc42 activity was manipulated in neurons through the acutely induced expression of two mutants of Cdc42 (Luo et al., 1994; Osterwalder et al., 2001): dominant-negative Cdc42(N17) for inhibiting endogenous activity by competing for upstream activators and…”
• Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. (2002, background): “In Drosophila, expression of constitutively active or dominant-negative DRac1 mutants block myoblast fusion; however, Drosophila Trio is not required for this step of myogenesis (Luo et al. 1994; Hakeda-Suzuki et al. 2002).”
• Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae. (2006, unknown): “When ChR2 was expressed panneuronally with the driver line elav-Gal4 [7], we observed instantaneous strong contractions of third instar larvae induced by blue light (see Movie S1 in the Supplemental Data available online).”
• A protein complex containing Inscuteable and the Gα-binding protein Pins orients asymmetric cell divisions in Drosophila (2000, unknown): “A Drosophila homologue of cdc42 has been identified [42], but a function in asymmetric cell division has not been demonstrated.”