Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Src, Fyn, and Yes are not required for neuromuscular synapse formation butare necessary for stabilization of agrin-induced clusters of acetylcholinereceptors
Autore:
Smith, CL; Mittaud, P; Prescott, ED; Fuhrer, C; Burden, SJ;
Indirizzi:
NYU, Sch Med, Mol Neurobiol Program, Sjirball Inst Biomol Med, New York, NY 10016 USA NYU New York NY USA 10016 jirball Inst Biomol Med, New York, NY 10016 USA Univ Zurich Irchel, Brain Res Inst, CH-8057 Zurich, Switzerland Univ Zurich Irchel Zurich Switzerland CH-8057 H-8057 Zurich, Switzerland
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 9, volume: 21, anno: 2001,
pagine: 3151 - 3160
SICI:
0270-6474(20010501)21:9<3151:SFAYAN>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOCAL ADHESION KINASE; EPSILON-SUBUNIT GENE; PROTEIN-TYROSINE KINASES; T-CELL ACTIVATION; FAMILY KINASES; MUTANT MICE; C-SRC; MAMMALIAN MUSCLE; IN-VIVO; SUBCELLULAR-LOCALIZATION;
Keywords:
AChR; Src; Yes; cytoskeleton; agrin; neuromuscular synapse;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
81
Recensione:
Indirizzi per estratti:
Indirizzo: Burden, SJ NYU, Sch Med, Mol Neurobiol Program, Sjirball Inst Biomol Med, New York, NY 10016 USA NYU New York NY USA 10016 t Biomol Med, New York, NY 10016 USA
Citazione:
C.L. Smith et al., "Src, Fyn, and Yes are not required for neuromuscular synapse formation butare necessary for stabilization of agrin-induced clusters of acetylcholinereceptors", J NEUROSC, 21(9), 2001, pp. 3151-3160

Abstract

Mice deficient in src and fyn or src and yes move and breathe poorly and die perinatally, consistent with defects in neuromuscular function. Src and Fyn are associated with acetylcholine receptors (AChRs) in muscle cells, and Src and Yes can act downstream of ErbB2, suggesting roles for Src family kinases in signaling pathways regulating neuromuscular synapse formation. We studied neuromuscular synapses in src(-/-); fyn(-/-) and src(-/-); yes(-/-) mutant mice and found that muscle development, motor axon pathfinding, clustering of postsynaptic proteins, and synapse-specific transcription are normal in these double mutants, showing that these pairs of kinases are notrequired for early steps in synapse formation. We generated muscle cell lines lacking src and fyn and found that neural agrin and laminin-1 induced normal clustering of AChRs and that agrin induced normal tyrosine phosphorylation of the AChR beta subunit in the absence of Src and Fyn. Another Src family member, most likely Yes, was associated with AChRs and phosphorylatedby agrin in myotubes lacking Src and Fyn, indicating that Yes may compensate for the loss of Src and Fyn. Nevertheless, PP1 and PP2, inhibitors of Src-class kinases, did not inhibit agrin signaling, suggesting that Src classkinase activity is dispensable for agrin-induced clustering and tyrosine phosphorylation of AChRs. AChR clusters, however, were less stable in myotubes lacking Src and Fyn but not in PP1- or PP2-treated wild-type cells. These data show that the stabilization of agrin-induced AChR clusters requires Src and Fyn and suggest that the adaptor activities, rather than the kinaseactivities, of these kinases are essential for this stabilization.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 07:49:10