Portal de Periódicos da CAPES

A kinase-deficient TrkC receptor isoform activates Arf6–Rac1 signaling through the scaffold protein tamalin

2006; Rockefeller University Press; Volume: 173; Issue: 2 Linguagem: Inglês

10.1083/jcb.200512013

1540-8140

Pedro F. Esteban, Hye‐Young Yoon, Jodi Becker, Susan G. Dorsey, Paola Caprari, Mary Ellen Palko, Vincenzo Coppola, H. Uri Saragovi, Paul A. Randazzo, Lino Tessarollo,

Axon Guidance and Neuronal Signaling

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.