Go/i Signaling is Involved in Facilitation of Neurite Outgrowth by Reelin

Abstract

The extracellular protein, reelin, which binds to ApoER2, VLDLR controls the positioning of radially migrating neurons and synaptic plasticity. During neurodevelopment activation of Go/i, a heterotrimeric G protein, facilitates the axon growth. Here we investigated the relationship between of Reelin signaling and Go/i during neurite formation of primary hippocampal neurons. In reeler, reelin‐deficient mice, neuritogenesis was significantly decreased. Inhibition of neuritogenesis in reeler was rescued by reelin treatment. The localization of Gαi1, Gαi3 and Gαo were obvious in the terminal portion of growing neurites in wild type, but not in reeler. In addition, treatment of pertussis toxin, Go/i inhibitor, suppressed the neurite formation by reelin. In study using F11 cells transfected Gαo mutant (Q205L), induction of neurite outgrowth by reelin could not be observed. To address the underlying mechanism, we investigated the downstream signaling pathway of reelin and Go/i using specific inhibitors. Reelin treatment induced the activation of MAPK‐JNK pathway, which is well‐known as a major pathway in neuritogenesis. Taken together, we suggest that Go/i signaling may be involved in induction of neuritogenesis by reelin.