Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway

Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study,...

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Veröffentlicht in:Experimental cell research 2004-10, Vol.299 (2), p.511-524
Hauptverfasser: Alleaume, Céline, Eychène, Alain, Harnois, Thomas, Bourmeyster, Nicolas, Constantin, Bruno, Caigneaux, Evelyne, Muller, Jean-Marc, Philippe, Michel
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container_end_page 524
container_issue 2
container_start_page 511
container_title Experimental cell research
container_volume 299
creator Alleaume, Céline
Eychène, Alain
Harnois, Thomas
Bourmeyster, Nicolas
Constantin, Bruno
Caigneaux, Evelyne
Muller, Jean-Marc
Philippe, Michel
description Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells.
doi_str_mv 10.1016/j.yexcr.2004.06.016
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SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. 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source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Cancer
Cdc42
cdc42 GTP-Binding Protein - metabolism
Cellular Biology
ERK
Genes, Dominant
Humans
Life Sciences
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - metabolism
Neurite remodeling
Neurites - drug effects
Neurites - metabolism
Neuroblastoma - metabolism
Neuroblastoma - pathology
Neuroprotective Agents - pharmacology
rac1 GTP-Binding Protein - metabolism
Ras
ras Proteins - metabolism
SH-SY5Y neuroblastoma cells
Signal Transduction
Subcellular Processes
Tumor Cells, Cultured
Vasoactive Intestinal Peptide - pharmacology
VIP
title Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway
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