A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin.
J Cell Biol
; 173(2): 291-9, 2006 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-16636148
ABSTRACT
Neurotrophins play an essential role in mammalian development. Most of their functions have been attributed to activation of the kinase-active Trk receptors and the p75 neurotrophin receptor. Truncated Trk receptor isoforms lacking the kinase domain are abundantly expressed during development and in the adult; however, their function and signaling capacity is largely unknown. We show that the neurotrophin-3 (NT3) TrkCT1-truncated receptor binds to the scaffold protein tamalin in a ligand-dependent manner. Moreover, NT3 initiation of this complex leads to activation of the Rac1 GTPase through adenosine diphosphate-ribosylation factor 6 (Arf6). At the cellular level, NT3 binding to TrkCT1-tamalin induces Arf6 translocation to the membrane, which in turn causes membrane ruffling and the formation of cellular protrusions. Thus, our data identify a new signaling pathway elicited by the kinase-deficient TrkCT1 receptor. Moreover, we establish NT3 as an upstream regulator of Arf6.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas de Transporte
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Fatores de Ribosilação do ADP
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Proteínas rac1 de Ligação ao GTP
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Receptor trkC
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article