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.
Scherer
S S
SS
Department of Neurology, University of Pennsylvania, Philadelphia 19104-6146.
Xu
Y T
YT
Roling
D
D
Wrabetz
L
L
Feltri
M L
ML
Kamholz
J
J
D000818:Animals; D001369:Axons / Q000502:physiology*; D015152:Blotting, Northern; D002450:Cell Communication; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects; D019922:GAP-43 Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000737:chemistry / Q000293:injuries / Q000502:physiology; D014855:Wallerian Degeneration
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D005576:Colforsin; D000242:Cyclic AMP