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

SACHDEV P; MENON S; KASTNER DB; CHUANG JZ; YEH TY; CONDE C; CÁCERES A; SUNG CH; SAKMAR TP

EMBO JOURNAL

Año: 2007 vol. 26 p. 2621 - 2632

0261-4189

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 Gbg-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 Gbg with Tctex-1 in neurite outgrowth. Ectopic expression of either Tctex-1 or Gbg promotes neurite outgrowth whereas interfering with their function inhibits neuritogenesis. Using embryonic mouse brain extracts, we demonstrate an endogenous Gbg–Tctex-1 complex and show that Gbg co-segregates with dynein free fractions of Tctex-1. Furthermore, Gb 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 Gbg and that Gbg–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.