RhoA regulates Schwann cell differentiation through JNK pathway

RhoA is a small GTPase that regulates many functions of mammalian cells via actin reorganization. Lots of studies uncovered that its activation acts as a major negative regulator of neurite extension, and inhibition of RhoA activity or reduction of its expression can promote neuron survival and axonal regeneration. However, little is known about whether RhoA also exerts important functions on Schwann cells (SCs) which are the glial cells of the peripheral nervous system (PNS). Recently, we reported that RhoA plays important roles in the proliferation, migration and myelination of SCs. In the present study, using RNA interference to knockdown RhoA expression and CT04 (a cell-permeable C3 Transferase) to inhibit RhoA activation we found that blocking RhoA can slack SC differentiation. Unexpectedly, inhibiting ROCK, the mostly well-known downstream effector of RhoA, has no influence on SC differentiation. Instead, the inhibition of RhoA in differentiating SCs results in the activation of JNK and p38 MAPK. And the inhibitor of JNK but not p38 MAPK can promote SC differentiation in the presence of RhoA inhibition. Overall results indicate that RhoA plays a vital role in SC differentiation via JNK pathway rather than ROCK pathway.