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Article

  • The EMBO Journal (2004) 23, 4792 - 4801
  • doi:10.1038/sj.emboj.7600418

Published online: 11 November 2004

Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis

Si Tuen Lee-Hoeflich1,a, Carrie G Causing2,a, Monika Podkowa3, Xin Zhao3, Jeffrey L Wrana2,4 and Liliana Attisano1,3

  1. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
  2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
  3. Department of Biochemistry, University of Toronto, Toronto, ON, Canada
  4. Department of Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada

Correspondence to:

Liliana Attisano, Department of Biochemistry, Medical Sciences Building, Room 6336, 1 King's College Circle, University of Toronto, Toronto, ON, Canada M5S 1A8. Tel.: +1 416 946 3129; Fax: +1 416 978 8548; E-mail: liliana.attisano@utoronto.ca

aThese authors contributed equally to this work

Received 27 July 2004; Accepted 31 August 2004

The growth and morphological differentiation of dendrites are critical events in the establishment of proper neuronal connectivity and neural function. One extrinsic factor, BMP7, has been shown to specifically affect dendritic morphogenesis; however, the underlying mechanism by which this occurs is unknown. Here we show that LIM kinase 1 (LIMK1), a key downstream effector of Rho GTPases, colocalizes with the BMP receptor, BMPRII, in the tips of neurites and binds to BMPRII. This interaction is required for BMP-dependent induction of the dendritic arbor in cortical neurons. Furthermore, we demonstrate that the physical interaction of LIMK1 with BMPRII synergizes with the Rho GTPase, Cdc42, to activate LIMK1 catalytic activity. These studies thus define a Smad-independent pathway that directly links the BMP receptor to regulation of actin dynamics and provides insights into how extracellular signals modulate LIMK1 activity to permit fine spatial control over cytoskeletal remodelling during dendritogenesis.

  • Keywords:

    • BMP,
    • dendritogenesis,
    • LIM kinase,
    • neuronal cells