RRC ID 31986
著者 Abe T, Yamazaki D, Murakami S, Hiroi M, Nitta Y, Maeyama Y, Tabata T.
タイトル The NAV2 homolog Sickie regulates F-actin-mediated axonal growth in Drosophila mushroom body neurons via the non-canonical Rac-Cofilin pathway.
ジャーナル Development
Abstract The Rac-Cofilin pathway is essential for cytoskeletal remodeling to control axonal development. Rac signals through the canonical Rac-Pak-LIMK pathway to suppress Cofilin-dependent axonal growth and through a Pak-independent non-canonical pathway to promote outgrowth. Whether this non-canonical pathway converges to promote Cofilin-dependent F-actin reorganization in axonal growth remains elusive. We demonstrate that Sickie, a homolog of the human microtubule-associated protein neuron navigator 2, cell-autonomously regulates axonal growth of Drosophila mushroom body (MB) neurons via the non-canonical pathway. Sickie was prominently expressed in the newborn F-actin-rich axons of MB neurons. A sickie mutant exhibited axonal growth defects, and its phenotypes were rescued by exogenous expression of Sickie. We observed phenotypic similarities and genetic interactions among sickie and Rac-Cofilin signaling components. Using the MARCM technique, distinct F-actin and phospho-Cofilin patterns were detected in developing axons mutant for sickie and Rac-Cofilin signaling regulators. The upregulation of Cofilin function alleviated the axonal defect of the sickie mutant. Epistasis analyses revealed that Sickie suppresses the LIMK overexpression phenotype and is required for Pak-independent Rac1 and Slingshot phosphatase to counteract LIMK. We propose that Sickie regulates F-actin-mediated axonal growth via the non-canonical Rac-Cofilin pathway in a Slingshot-dependent manner.
巻・号 141(24)
ページ 4716-28
公開日 2014-12-1
DOI 10.1242/dev.113308
PII dev.113308
PMID 25411210
MeSH Actin Depolymerizing Factors / metabolism* Actins / metabolism* Animals Axons / metabolism Axons / physiology* Drosophila / growth & development* Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism* Immunohistochemistry Lim Kinases / metabolism Mushroom Bodies / cytology* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phosphoprotein Phosphatases / metabolism Signal Transduction / physiology* rac1 GTP-Binding Protein / metabolism*
IF 5.611
引用数 17
WOS 分野 DEVELOPMENTAL BIOLOGY
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