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
|
リソース情報 |
ショウジョウバエ |
|