Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth

Yi Xie, Yu Qiang Ding, Yan Hong, Zhu Feng, Sammy Navarre, Caixia Xi, Xiao Juan Zhu, Chun Lei Wang, S. L. Ackerman, David J Kozlowski, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.

Original languageEnglish (US)
Pages (from-to)1124-1132
Number of pages9
JournalNature Cell Biology
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2005

Fingerprint

Phospholipid Transfer Proteins
Neurites
Colorectal Neoplasms
Hydrolysis
Embryonic Structures
Neurons
Morpholinos
Neuronal Outgrowth
netrin-1
Motor Neurons
Zebrafish
Phosphatidylinositols
Protein Binding
Nervous System
Cues
Axons
Chickens
Spinal Cord
Lipids

ASJC Scopus subject areas

  • Cell Biology

Cite this

Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth. / Xie, Yi; Ding, Yu Qiang; Hong, Yan; Feng, Zhu; Navarre, Sammy; Xi, Caixia; Zhu, Xiao Juan; Wang, Chun Lei; Ackerman, S. L.; Kozlowski, David J; Mei, Lin; Xiong, Wencheng.

In: Nature Cell Biology, Vol. 7, No. 11, 01.11.2005, p. 1124-1132.

Research output: Contribution to journalArticle

Xie, Y, Ding, YQ, Hong, Y, Feng, Z, Navarre, S, Xi, C, Zhu, XJ, Wang, CL, Ackerman, SL, Kozlowski, DJ, Mei, L & Xiong, W 2005, 'Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth', Nature Cell Biology, vol. 7, no. 11, pp. 1124-1132. https://doi.org/10.1038/ncb1321
Xie, Yi ; Ding, Yu Qiang ; Hong, Yan ; Feng, Zhu ; Navarre, Sammy ; Xi, Caixia ; Zhu, Xiao Juan ; Wang, Chun Lei ; Ackerman, S. L. ; Kozlowski, David J ; Mei, Lin ; Xiong, Wencheng. / Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth. In: Nature Cell Biology. 2005 ; Vol. 7, No. 11. pp. 1124-1132.
@article{2832943da3fb454797a5d39a2b21bdf0,
title = "Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth",
abstract = "Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.",
author = "Yi Xie and Ding, {Yu Qiang} and Yan Hong and Zhu Feng and Sammy Navarre and Caixia Xi and Zhu, {Xiao Juan} and Wang, {Chun Lei} and Ackerman, {S. L.} and Kozlowski, {David J} and Lin Mei and Wencheng Xiong",
year = "2005",
month = "11",
day = "1",
doi = "10.1038/ncb1321",
language = "English (US)",
volume = "7",
pages = "1124--1132",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth

AU - Xie, Yi

AU - Ding, Yu Qiang

AU - Hong, Yan

AU - Feng, Zhu

AU - Navarre, Sammy

AU - Xi, Caixia

AU - Zhu, Xiao Juan

AU - Wang, Chun Lei

AU - Ackerman, S. L.

AU - Kozlowski, David J

AU - Mei, Lin

AU - Xiong, Wencheng

PY - 2005/11/1

Y1 - 2005/11/1

N2 - Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.

AB - Neurite extension is essential for wiring the nervous system during development. Although several factors are known to regulate neurite outgrowth, the underlying mechanisms remain unclear. Here, we provide evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue. PITPα interacts with the netrin receptor DCC (deleted in colorectal cancer) and neogenin. Netrin-1 stimulates PITPα binding to DCC and to phosphatidylinositol (5) phosphate [PI(5)P], increases its lipid-transfer activity and elevates hydrolysis of phosphatidylinositol bisphosphate (PIP2). In addition, the stimulated PIP2 hydrolysis requires PITPα. Furthermore, cortical explants of PITPα mutant mice are defective in extending neurites in response to netrin-1. Commissural neurons from chicken embryos expressing a dominant-negative PITPα mutant show reduced axon outgrowth. Morpholino-mediated knockdown of PITPα expression in zebrafish embryos leads to dose-dependent defects in motor-neuron axons and reduced numbers of spinal-cord neurons. Taken together, these results identify a crucial role for PITPα in netrin-1-induced neurite outgrowth, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.

UR - http://www.scopus.com/inward/record.url?scp=33644832752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644832752&partnerID=8YFLogxK

U2 - 10.1038/ncb1321

DO - 10.1038/ncb1321

M3 - Article

VL - 7

SP - 1124

EP - 1132

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 11

ER -