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  • The EMBO Journal (2007) 26, 2621 - 2632
  • doi:10.1038/sj.emboj.7601716

Published online: 10 May 2007

G protein bold betabig gamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth

Pallavi Sachdev1, Santosh Menon1, David B Kastner1,a, Jen-Zen Chuang2, Ting-Yu Yeh2,b, Cecilia Conde3, Alfredo Caceres3, Ching-Hwa Sung2,4 and Thomas P Sakmar1

  1. Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, New York, NY, USA
  2. Department of Ophthalmology, Weill Medical College of Cornell University, New York, NY, USA
  3. INIMEC-CONICET, Cordoba, Argentina
  4. Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY, USA

Correspondence to:

Thomas P Sakmar, Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, 1230 York Avenue, Box 187, New York City, NY 10021, USA. Tel.: +1 212 327 8288; Fax: +1 212 327 7904; E-mail: sakmar@rockefeller.edu

aPresent address: Stanford University Medical School, Palo Alto, CA 94305, USA

bPresent address: Johns Hopkins University, Baltimore, MD 21218, USA

Received 16 August 2006; Accepted 12 April 2007

Tctex-1, a light-chain component of the cytoplasmic dynein motor complex, can function independently of dynein to regulate multiple steps in neuronal development. However, how dynein-associated and dynein-free pools of Tctex-1 are maintained in the cell is not known. Tctex-1 was recently identified as a Gbetagamma-binding protein and shown to be identical to the receptor-independent activator of G protein signaling AGS2. We propose a novel role for the interaction of Gbetagamma with Tctex-1 in neurite outgrowth. Ectopic expression of either Tctex-1 or Gbetagamma promotes neurite outgrowth whereas interfering with their function inhibits neuritogenesis. Using embryonic mouse brain extracts, we demonstrate an endogenous Gbetagamma–Tctex-1 complex and show that Gbetagamma co-segregates with dynein-free fractions of Tctex-1. Furthermore, Gbeta competes with the dynein intermediate chain for binding to Tctex-1, regulating assembly of Tctex-1 into the dynein motor complex. We propose that Tctex-1 is a novel effector of Gbetagamma, and that Gbetagamma–Tctex-1 complex plays a key role in the dynein-independent function of Tctex-1 in regulating neurite outgrowth in primary hippocampal neurons, most likely by modulating actin and microtubule dynamics.

  • Keywords:

    • AGS,
    • dynein,
    • heterotrimeric G protein,
    • neurite outgrowth