The RhoGAP activity of OPHN1, a new F-actin-binding protein, is negatively controlled by its amino-terminal domain

Fabien Fauchereau; Ulrike Herbrand; Philippe Chafey; Alexander Eberth; Annette Koulakoff; Marie-Claude Vinet; Mohammad Reza Ahmadian; Jamel Chelly; Pierre Billuart

doi:10.1016/s1044-7431(03)00078-2

The RhoGAP activity of OPHN1, a new F-actin-binding protein, is negatively controlled by its amino-terminal domain

Mol Cell Neurosci. 2003 Aug;23(4):574-86. doi: 10.1016/s1044-7431(03)00078-2.

Authors

Fabien Fauchereau¹, Ulrike Herbrand, Philippe Chafey, Alexander Eberth, Annette Koulakoff, Marie-Claude Vinet, Mohammad Reza Ahmadian, Jamel Chelly, Pierre Billuart

Affiliation

¹ Institut Cochin, INSERM U567, CNRS UMR8104, Université Paris V René Descartes, IFR116, 24 rue du Fg St Jacques, 75014, Paris, France.

PMID: 12932438
DOI: 10.1016/s1044-7431(03)00078-2

Abstract

Recent human genetic approaches showed that mutations in three genes encoding OPHN1, PAK3, and alphaPIX cause nonspecific X-linked mental retardation. These three proteins act to modulate Rho GTPase signaling pathways and may participate in neuronal morphogenesis by regulating the actin cytoskeleton. Here we showed that the Oligophrenin-1 gene is expressed in the developing spinal cord and later in brain areas that are characterized by high synaptic plasticity. At the cellular level OPHN1 is expressed in both glial and neuronal cells where it colocalizes with actin, notably at the tip of growing neurites. This interaction seems to be direct through a novel uncharacterized domain in the carboxyl-terminal end of OPHN1. Overexpression experiments in fibroblasts showed that the OPHN1 RhoGAP domain regulates in vivo the actin cytoskeleton by inhibition of Rho pathways. Interestingly the amino-terminal domain of OPHN1 inhibits the RhoGAP activity through an as yet unknown mechanism, suggesting that OPHN1 may be tightly regulated in vivo.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Actin Cytoskeleton / metabolism*
Animals
COS Cells
Central Nervous System / abnormalities*
Central Nervous System / cytology
Central Nervous System / metabolism*
Cytoskeletal Proteins*
Feedback, Physiological / genetics
Fetus
GTPase-Activating Proteins / genetics
GTPase-Activating Proteins / metabolism*
Gene Expression Regulation, Developmental / drug effects
Gene Expression Regulation, Developmental / genetics
Intellectual Disability / genetics
Intellectual Disability / metabolism
Mice
Neurites / metabolism*
Neurites / ultrastructure
Neuroglia / metabolism*
Neuroglia / ultrastructure
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Protein Binding / genetics
Protein Structure, Tertiary / genetics
Rats
cdc42 GTP-Binding Protein / genetics
cdc42 GTP-Binding Protein / metabolism
rac1 GTP-Binding Protein / genetics
rac1 GTP-Binding Protein / metabolism
rhoA GTP-Binding Protein / genetics
rhoA GTP-Binding Protein / metabolism

Substances

Cytoskeletal Proteins
GTPase-Activating Proteins
Nuclear Proteins
Ophn1 protein, mouse
Phosphoproteins
rho GTPase-activating protein
cdc42 GTP-Binding Protein
rac1 GTP-Binding Protein
rhoA GTP-Binding Protein