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Publication : G protein beta gamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth.

First Author  Sachdev P Year  2007
Journal  EMBO J Volume  26
Issue  11 Pages  2621-32
PubMed ID  17491591 Mgi Jnum  J:162216
Mgi Id  MGI:4818336 Doi  10.1038/sj.emboj.7601716
Citation  Sachdev P, et al. (2007) G protein beta gamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth. EMBO J 26(11):2621-32
abstractText  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.
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