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Titolo:
p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation
Autore:
Brouns, MR; Matheson, SF; Settleman, J;
Indirizzi:
Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA Massachusetts Gen Hosp Boston MA USA 02129 Canc Ctr, Boston, MA 02129 USA Harvard Univ, Sch Med, Boston, MA 02129 USA Harvard Univ Boston MA USA 02129 vard Univ, Sch Med, Boston, MA 02129 USA
Titolo Testata:
NATURE CELL BIOLOGY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 361 - 367
SICI:
1465-7392(200104)3:4<361:PRITPS>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
LONG-TERM POTENTIATION; GTPASE-ACTIVATING PROTEIN; CENTRAL-NERVOUS-SYSTEM; TYROSINE KINASES; MUTANT MICE; C-SRC; NEURITE OUTGROWTH; COMMISSURAL AXONS; CELL-ADHESION; GENE-PRODUCT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Settleman, J Massachusetts Gen Hosp, MGH Canc Ctr, 149 13th St, Boston, MA02129 USA Massachusetts Gen Hosp 149 13th St Boston MA USA 02129 29 USA
Citazione:
M.R. Brouns et al., "p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation", NAT CELL BI, 3(4), 2001, pp. 361-367

Abstract

The Src tyrosine kinases have been implicated in several aspects of neuraldevelopment and nervous system function; however, their relevant substrates in brain and their mechanism of action in neurons remain to be established clearly. Here we identify the potent Rho regulatory protein, p190 RhoGAP (GTPase-activating protein), as the principal Src substrate detected in thedeveloping and mature nervous system. We also find that mice lacking functional p190 RhoGAP exhibit defects in axon guidance and fasciculation, p190 RhoGAP is cc-enriched with F-actin in the distal tips of axons, and overexpressing p190 RhoGAP in neuroblastoma cells promotes extensive neurite outgrowth, indicating that p190 RhoGAP may be an important regulator of Rho-mediated actin reorganization in neuronal growth cones. p190 RhoGAP transduces signals downstream of cell-surface adhesion molecules, and we find that p190-RhoGAP-mediated neurite outgrowth is promoted by the extracellular matrixprotein laminin. Together with the fact that mice lacking neural adhesion molecules or Src kinases also exhibit defects in axon outgrowth, guidance and fasciculation, our results suggest that p190 RhoGAP mediates a Src-dependent adhesion signal for neuritogenesis to the actin cytoskeleton through the Rho GTPase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 13:38:37