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

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 G beta gamma-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 G beta gamma with Tctex-1 in neurite outgrowth. Ectopic expression of either Tctex-1 or G beta gamma promotes neurite outgrowth whereas interfering with their function inhibits neuritogenesis. Using embryonic mouse brain extracts, we demonstrate an endogenous G beta gamma-Tctex-1 complex and show that G beta gamma 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 G beta gamma, and that G beta gamma-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.