Neuronal regeneration enhances the expression of the immunophilin FKBP-12.
Immunophilins are a group of proteins that serve as receptors for the immunosuppressant drugs cyclosporin A and FK506. The immunophilin designated FK-506 binding protein-12 (FKBP-12) is concentrated more than 10 times higher in the brain than in immune tissues. The complex of FK506 and FKBP-12 inhibits the calcium activated phosphatase, calcineurin, increasing phosphorylated levels of calcineurin substrates with growth associated protein-43 (GAP-43), being most prominent in the brain. We now demonstrate an association of FKBP-12 with neuronal regeneration and GAP-43 disposition. Facial nerve crush markedly augments expression of FKBP-12 mRNA in the facial nucleus with a time course paralleling changes in GAP-43 mRNA. Following sciatic nerve lesions, similar increases in FKBP-12 mRNA occur in lumbar motor neurons and dorsal root ganglia neuronal cells. Increased FKBP-12 expression appears linked to regeneration rather than degeneration as facial nerve lesions elicited by ricin injection, which produce neuronal death without regeneration, fail to augment FKBP-12 expression in the facial nucleus. The time course for accumulation of FKBP-12 in sciatic nerve segments following nerve crush indicates rapid axonal transport at a rate similar to GAP-43.
Lyons
W E
WE
Division of Toxicological Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA.
Steiner
J P
JP
Snyder
S H
SH
Dawson
T M
TM
D000375:Aging / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005154:Facial Nerve / Q000502:physiology; D019922:GAP-43 Protein; D005727:Ganglia, Spinal / Q000502:physiology*; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D009046:Motor Neurons / Q000502:physiology; D009409:Nerve Crush; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000502:physiology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology*; D016559:Tacrolimus / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D019922:GAP-43 Protein; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus