Expression of growth‐associated protein‐43 kD in Schwann cells is regulated by axon‐Schwann cell interactions and cAMP

We have examined the regulation of growth‐associated protein 43 kD (GAP‐43) in rat Schwann cells. In unlesioned adult nerves, GAP‐43‐immunoreactivity was restricted to non‐myelinating Schwann cells and unmyelinated axons. When adult nerves were transected to cause permanent axotomy, previously myelinating Schwann cells expressed progressively more GAP‐43‐immunoreactivity over 3 weeks and GAP‐43 mRNA levels increased over a similar time course. The peak level of GAP‐43 mRNA occurred at least 2 weeks later than that of nerve growth factor receptor, another marker of denervated Schwann cells. In contrast, after nerve‐crush, which allows axonal regeneration, many fewer Schwann cells had GAP‐43‐immunoreactivity, and the amount of GAP‐43 mRNA was markedly lower than in transected nerves. Forskolin, a drug that activates adenylate cyclase and mimics many effects of axon‐Schwann cell interactions, markedly reduced GAP‐43‐immunoreactivity and mRNA expression in cultured Schwann cells, whereas interleukin‐1 had no effect. These data demonstrate that axon‐Schwann cell interactions inhibit the expression of GAP‐43 in Schwann cells and that this effect is mimicked by forskolin. © 1994 Wiley‐Liss, Inc.