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

J. Cell Biol., 24 April 2006
Vol. 173, Issue 2, p. 291-299
DOI: 10.1083/jcb.200512013

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

  1. Pedro F. Esteban1,
  2. Hye-Young Yoon2,
  3. Jodi Becker1,
  4. Susan G. Dorsey1,
  5. Paola Caprari1,
  6. Mary Ellen Palko1,
  7. Vincenzo Coppola1,
  8. H. Uri Saragovi3,
  9. Paul A. Randazzo2, and
  10. Lino Tessarollo1
  1. 1Neural Development Group, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21702
  2. 2Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892
  3. 3Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1Y6
  1. Correspondence to Lino Tessarollo: tessarol{at}ncifcrf.gov

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.

  • Submitted: 2 December 2005
  • Accepted: 20 March 2006

Citation:

P. F. Esteban, H.-Y. Yoon, J. Becker, S. G. Dorsey, P. Caprari, M. E. Palko, V. Coppola, H. U. Saragovi, P. A. Randazzo, and L. Tessarollo, A kinase-deficient TrkC receptor isoform activates Arf6–Rac1 signaling through the scaffold protein tamalin. J. Cell Biol. 173, 291-299 (2006).

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