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