Rho GTPases regulate axon growth through convergent and divergent signaling pathways

Julian Ng; Liqun Luo

doi:10.1016/j.neuron.2004.11.014

Rho GTPases regulate axon growth through convergent and divergent signaling pathways

Julian Ng, Liqun Luo

King's College London

Research output: Contribution to journal › Article › peer-review

164 Citations (Scopus)

Abstract

Rho GTPases are essential regulators of cytoskeletal reorganization, but how they do so during neuronal morphogenesis in vivo is poorly understood. Here we show that the actin depolymerization factor cofilin is essential for axon growth in Drosophila neurons. Cofilin function in axon growth is inhibited by LIM kinase and activated by Slingshot phosphatase. Dephosphorylating cofilin appears to be the major function of Slingshot in regulating axon growth in vivo. Genetic data provide evidence that Rho or Rac/Cdc42, via effector kinases Rok or Pak, respectively, activate LIM kinase to inhibit axon growth. Importantly, Rac also activates a Pak-independent pathway that promotes axon growth, and different RacGEFs regulate these distinct pathways. These genetic analyses reveal convergent and divergent pathways from Rho GTPases to the cytoskeleton during axon growth in vivo and suggest that different developmental outcomes could be achieved by biases in pathway selection.

Original language	English
Pages (from-to)	779 - 793
Number of pages	15
Journal	Neuron
Volume	44
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2004.11.014
Publication status	Published - 2 Dec 2004

Access to Document

10.1016/j.neuron.2004.11.014

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSS-4DXJJ0V-7&_user=121727&_coverDate=12%2F02%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000010000&_version=1&_urlVersion=0&_userid=121727&md5=066425c18750690bf48b7364d46a9d29

Cite this

@article{d0549a052b12422daf0fbe0679904a23,

title = "Rho GTPases regulate axon growth through convergent and divergent signaling pathways",

abstract = "Rho GTPases are essential regulators of cytoskeletal reorganization, but how they do so during neuronal morphogenesis in vivo is poorly understood. Here we show that the actin depolymerization factor cofilin is essential for axon growth in Drosophila neurons. Cofilin function in axon growth is inhibited by LIM kinase and activated by Slingshot phosphatase. Dephosphorylating cofilin appears to be the major function of Slingshot in regulating axon growth in vivo. Genetic data provide evidence that Rho or Rac/Cdc42, via effector kinases Rok or Pak, respectively, activate LIM kinase to inhibit axon growth. Importantly, Rac also activates a Pak-independent pathway that promotes axon growth, and different RacGEFs regulate these distinct pathways. These genetic analyses reveal convergent and divergent pathways from Rho GTPases to the cytoskeleton during axon growth in vivo and suggest that different developmental outcomes could be achieved by biases in pathway selection.",

author = "Julian Ng and Liqun Luo",

year = "2004",

month = dec,

day = "2",

doi = "10.1016/j.neuron.2004.11.014",

language = "English",

volume = "44",

pages = "779 -- 793",

journal = "Neuron",

publisher = "CELL PRESS",

number = "5",

}

TY - JOUR

T1 - Rho GTPases regulate axon growth through convergent and divergent signaling pathways

AU - Ng, Julian

AU - Luo, Liqun

PY - 2004/12/2

Y1 - 2004/12/2

N2 - Rho GTPases are essential regulators of cytoskeletal reorganization, but how they do so during neuronal morphogenesis in vivo is poorly understood. Here we show that the actin depolymerization factor cofilin is essential for axon growth in Drosophila neurons. Cofilin function in axon growth is inhibited by LIM kinase and activated by Slingshot phosphatase. Dephosphorylating cofilin appears to be the major function of Slingshot in regulating axon growth in vivo. Genetic data provide evidence that Rho or Rac/Cdc42, via effector kinases Rok or Pak, respectively, activate LIM kinase to inhibit axon growth. Importantly, Rac also activates a Pak-independent pathway that promotes axon growth, and different RacGEFs regulate these distinct pathways. These genetic analyses reveal convergent and divergent pathways from Rho GTPases to the cytoskeleton during axon growth in vivo and suggest that different developmental outcomes could be achieved by biases in pathway selection.

AB - Rho GTPases are essential regulators of cytoskeletal reorganization, but how they do so during neuronal morphogenesis in vivo is poorly understood. Here we show that the actin depolymerization factor cofilin is essential for axon growth in Drosophila neurons. Cofilin function in axon growth is inhibited by LIM kinase and activated by Slingshot phosphatase. Dephosphorylating cofilin appears to be the major function of Slingshot in regulating axon growth in vivo. Genetic data provide evidence that Rho or Rac/Cdc42, via effector kinases Rok or Pak, respectively, activate LIM kinase to inhibit axon growth. Importantly, Rac also activates a Pak-independent pathway that promotes axon growth, and different RacGEFs regulate these distinct pathways. These genetic analyses reveal convergent and divergent pathways from Rho GTPases to the cytoskeleton during axon growth in vivo and suggest that different developmental outcomes could be achieved by biases in pathway selection.

U2 - 10.1016/j.neuron.2004.11.014

DO - 10.1016/j.neuron.2004.11.014

M3 - Article

VL - 44

SP - 779

EP - 793

JO - Neuron

JF - Neuron

IS - 5

ER -

Rho GTPases regulate axon growth through convergent and divergent signaling pathways

Abstract

Access to Document

Fingerprint

Cite this