GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

TableEdit

Jump to: navigation, search

PMID:18331715

You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor

Citation

Shen, Y, Li, N, Wu, S, Zhou, Y, Shan, Y, Zhang, Q, Ding, C, Yuan, Q, Zhao, F, Zeng, R and Zhu, X (2008) Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev. Cell 14:342-53

Abstract

Cdc42GAP promotes inactivation of Cdc42, a small GTPase whose activation at the leading edge by guanine nucleotide exchange factors is critical for cell migration. How Cdc42GAP is regulated to ensure proper levels of active Cdc42 is poorly understood. Here we show that Nudel, a cytoplasmic dynein regulator, competes with Cdc42 for binding Cdc42GAP. Consequently, Nudel can inhibit Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner. Both Nudel and Cdc42GAP exhibit leading-edge localization in migrating cells. The localization of Nudel requires its phosphorylation by Erk1/2. Depleting Nudel by RNAi or overexpression of a nonphosphorylatable mutant abolishes Cdc42 activation and cell migration. Our data thus uncover Nudel as a regulator of Cdc42 during cell migration. Nudel facilitates cell migration by sequestering Cdc42GAP at the leading edge to stabilize active Cdc42 in response to extracellular stimuli. Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP from Nudel.

Links

PubMed Online version:10.1016/j.devcel.2008.01.001

Keywords

Animals; Carrier Proteins/antagonists & inhibitors; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cell Movement/physiology; Cell Polarity; Centrosome/metabolism; Dyneins/metabolism; GTPase-Activating Proteins/genetics; GTPase-Activating Proteins/metabolism; Humans; Mice; Models, Biological; Mutation; NIH 3T3 Cells; Phosphorylation; Protein Binding; RNA Interference; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; cdc42 GTP-Binding Protein/genetics; cdc42 GTP-Binding Protein/metabolism

public



Cancel