dc.description.abstract | Gas7 (Growth arrest-specific gene 7) was isolated in growth-arrested NIH3T3 cells upon serum starvation or growth confluence. Gas7 is highly expressed in the mouse testis and brain, mostly in the hippocampus, cortex, and Purkinje neurons of cerebellum. Previous data showed that Gas7 is required for the neuronal differentiation of terminally differentiated Purkinje cells and differentiation of PC12 upon NGF stimulation. Biochemical studies also showed that Gas7 functions with actin to enhance actin polymerization and crosslinking the actin filaments through Gas7 C-termini, resulting in membrane ruffles in the cells. However, the role of Gas7 in the neurons remained unclear. Here, we tried to determine the role of Gas7 in neurons through determination of its interacting proteins. First, N-WASP was discovered as a novel Gas7-interacting protein through its interaction with WISH, another Gas7-interacting protein. We obtained clear evidence that Gas7 functions directly with N-WASP, via WW-Pro interaction, to regulate actin dynamics in a Cdc42-independent manner in the cells. Our data show that this specific interaction is indispensable for regular neurite outgrowth of hippocampal neurons. Second, another Gas7-interacting protein, Gas7CIP1/CDK5RAP2, from yeast two-hybrid system screening was characterized to assess indirectly the role of Gas7 in the cells. The data showed that CDK5RAP2 is centrosome-associated protein and acts as a scaffold to recruit γ-tubulin. CDK5RAP2 contributes to the maturation of centrosome and affects the cell cycle. Furthermore, we found that CDK5RAP2 is distributed in the centrosome of developing hippocampal neurons during early stages of development. The centrosome regulates neuronal differentiation or migration processes through the regulation of microtubule dynamics in neurons. Therefore, our data implicate that CDK5RAP2 may play a role in the regulation of microtubule dynamics to affect the neuronal differentiation or migration, especially nucleokinesis. However, how CDK5RAP2 functions in the neurons still awaits further investigation. Overall, this study clearly showed how Gas7 functions with N-WASP to regulate the neurite outgrowth of hippocampal neurons, thus providing the possibility that Gas7 may function together with CDK5RAP2 to regulate microtubule dynamics in neurons to control neuronal differentiation or migration. | en |