PortalPublikationenThe neural cell adhesion molecule (NCAM) associates with and...

The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1)

Standard

The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1). / Li, Shen; Leshchyns´ka, Iryna; Chernyshova, Yana; Schachner, Melitta; Sytnyk, Vladimir.

in: J NEUROSCI, Jahrgang 33, Nr. 2, 09.01.2013, S. 790-803.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Li, S, Leshchyns´ka, I, Chernyshova, Y, Schachner, M & Sytnyk, V 2013, 'The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1)', J NEUROSCI, Jg. 33, Nr. 2, S. 790-803. https://doi.org/10.1523/JNEUROSCI.1238-12.2013

APA

Li, S., Leshchyns´ka, I., Chernyshova, Y., Schachner, M., & Sytnyk, V. (2013). The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1). J NEUROSCI, 33(2), 790-803. https://doi.org/10.1523/JNEUROSCI.1238-12.2013

Vancouver

Li S, Leshchyns´ka I, Chernyshova Y, Schachner M, Sytnyk V. The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1). J NEUROSCI. 2013 Jan 9;33(2):790-803. https://doi.org/10.1523/JNEUROSCI.1238-12.2013

Bibtex

@article{773a551eb3724a7bb5938f39c34c928e,
title = "The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1)",
abstract = "The Neural cell adhesion molecule (NCAM) plays an important role in regulation of nervous system development. To expand our understanding of the molecular mechanisms via which NCAM influences differentiation of neurons, we used a yeast two-hybrid screening to search for new binding partners of NCAM and identified p21-activated kinase 1 (Pak1). We show that NCAM interacts with Pak1 in growth cones of neurons. The autophosphorylation and activity of Pak1 were enhanced when isolated growth cones were incubated with NCAM function triggering antibodies, which mimic the interaction between NCAM and its extracellular ligands. The association of Pak1 with cell membranes, the efficiency of Pak1 binding to its activators, and Pak1 activity were inhibited in brains of NCAM-deficient mice. NCAM-dependent Pak1 activation was abolished after lipid raft disruption, suggesting that NCAM promotes Pak1 activation in the lipid raft environment. Phosphorylation of the downstream Pak1 effectors LIMK1 and cofilin was reduced in growth cones from NCAM-deficient neurons, which was accompanied by decreased levels of filamentous actin and inhibited filopodium mobility in the growth cones. Dominant-negative Pak1 inhibited and constitutively active Pak1 enhanced the ability of neurons to increase neurite outgrowth in response to the extracellular ligands of NCAM. Our combined observations thus indicate that NCAM activates Pak1 to drive actin polymerization to promote neuronal differentiation.",
keywords = "Actins, Animals, Antibodies, Monoclonal, Brain Chemistry, Cells, Cultured, Cerebral Cortex, Cytoskeleton, DNA, Female, Growth Cones, Hippocampus, Immunoprecipitation, Male, Membrane Microdomains, Mice, Mice, Inbred C57BL, Mice, Knockout, Neural Cell Adhesion Molecules, Neurites, Phosphorylation, Rats, Saccharomyces cerevisiae, Signal Transduction, cdc42 GTP-Binding Protein, p21-Activated Kinases",
author = "Shen Li and Iryna Leshchyns´ka and Yana Chernyshova and Melitta Schachner and Vladimir Sytnyk",
year = "2013",
month = jan,
day = "9",
doi = "10.1523/JNEUROSCI.1238-12.2013",
language = "English",
volume = "33",
pages = "790--803",
journal = "J NEUROSCI",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "2",

}

RIS

TY - JOUR

T1 - The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1)

AU - Li, Shen

AU - Leshchyns´ka, Iryna

AU - Chernyshova, Yana

AU - Schachner, Melitta

AU - Sytnyk, Vladimir

PY - 2013/1/9

Y1 - 2013/1/9

N2 - The Neural cell adhesion molecule (NCAM) plays an important role in regulation of nervous system development. To expand our understanding of the molecular mechanisms via which NCAM influences differentiation of neurons, we used a yeast two-hybrid screening to search for new binding partners of NCAM and identified p21-activated kinase 1 (Pak1). We show that NCAM interacts with Pak1 in growth cones of neurons. The autophosphorylation and activity of Pak1 were enhanced when isolated growth cones were incubated with NCAM function triggering antibodies, which mimic the interaction between NCAM and its extracellular ligands. The association of Pak1 with cell membranes, the efficiency of Pak1 binding to its activators, and Pak1 activity were inhibited in brains of NCAM-deficient mice. NCAM-dependent Pak1 activation was abolished after lipid raft disruption, suggesting that NCAM promotes Pak1 activation in the lipid raft environment. Phosphorylation of the downstream Pak1 effectors LIMK1 and cofilin was reduced in growth cones from NCAM-deficient neurons, which was accompanied by decreased levels of filamentous actin and inhibited filopodium mobility in the growth cones. Dominant-negative Pak1 inhibited and constitutively active Pak1 enhanced the ability of neurons to increase neurite outgrowth in response to the extracellular ligands of NCAM. Our combined observations thus indicate that NCAM activates Pak1 to drive actin polymerization to promote neuronal differentiation.

AB - The Neural cell adhesion molecule (NCAM) plays an important role in regulation of nervous system development. To expand our understanding of the molecular mechanisms via which NCAM influences differentiation of neurons, we used a yeast two-hybrid screening to search for new binding partners of NCAM and identified p21-activated kinase 1 (Pak1). We show that NCAM interacts with Pak1 in growth cones of neurons. The autophosphorylation and activity of Pak1 were enhanced when isolated growth cones were incubated with NCAM function triggering antibodies, which mimic the interaction between NCAM and its extracellular ligands. The association of Pak1 with cell membranes, the efficiency of Pak1 binding to its activators, and Pak1 activity were inhibited in brains of NCAM-deficient mice. NCAM-dependent Pak1 activation was abolished after lipid raft disruption, suggesting that NCAM promotes Pak1 activation in the lipid raft environment. Phosphorylation of the downstream Pak1 effectors LIMK1 and cofilin was reduced in growth cones from NCAM-deficient neurons, which was accompanied by decreased levels of filamentous actin and inhibited filopodium mobility in the growth cones. Dominant-negative Pak1 inhibited and constitutively active Pak1 enhanced the ability of neurons to increase neurite outgrowth in response to the extracellular ligands of NCAM. Our combined observations thus indicate that NCAM activates Pak1 to drive actin polymerization to promote neuronal differentiation.

KW - Actins

KW - Animals

KW - Antibodies, Monoclonal

KW - Brain Chemistry

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Cytoskeleton

KW - DNA

KW - Female

KW - Growth Cones

KW - Hippocampus

KW - Immunoprecipitation

KW - Male

KW - Membrane Microdomains

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neural Cell Adhesion Molecules

KW - Neurites

KW - Phosphorylation

KW - Rats

KW - Saccharomyces cerevisiae

KW - Signal Transduction

KW - cdc42 GTP-Binding Protein

KW - p21-Activated Kinases

U2 - 10.1523/JNEUROSCI.1238-12.2013

DO - 10.1523/JNEUROSCI.1238-12.2013

M3 - SCORING: Journal article

C2 - 23303955

VL - 33

SP - 790

EP - 803

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 2

ER -