cAMP ‐induced activation of protein kinase A and p190B RhoGAP mediates down‐regulation of TC10 activity at the plasma membrane and neurite outgrowth

Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP‐induced signaling leading to the regulation of membrane trafficking remains unknown. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF‐treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP addition in neuronal cells. TC10 was locally inactivated at extending neurite tips in cAMP‐treated PC12 cells. TC10 depletion led to a decrease in cAMP‐induced neurite outgrowth. Constitutively active TC10 could not rescue this growth reduction, supporting our model for a role of GTP hydrolysis of TC10 in neuritogenesis by accelerating vesicle fusion. The cAMP‐induced TC10 inactivation was mediated by PKA. Considering cAMP‐induced RhoA inactivation, we found that p190B, but not p190A, mediated inactivation of TC10 and RhoA. Upon cAMP treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1‐N17 expression reduced cAMP‐induced TC10 inactivation. Together, the PKA‐STEF‐Rac1‐p190B pathway leading to inactivation of TC10 and RhoA at the plasma membrane plays an important role in cAMP‐induced neurite outgrowth.

Here, we demonstrated that cAMP‐induced down‐regulation of plasmalemmal TC10 and RhoA ...

Source: Genes to Cells - October 1, 2017 Category: Genetics & Stem Cells Authors: Shingo Koinuma, Kohei Takeuchi, Naoyuki Wada, Takeshi Nakamura Tags: ORIGINAL ARTICLE Source Type: research