Neuronal regeneration enhances the expression of the immunophilin FKBP-12

W. Ernest Lyons, Joseph P. Steiner, Solomon H. Snyder, Ted M. Dawson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2985-2994
Number of pages10
JournalJournal of Neuroscience
Volume15
Issue number4
DOIs
StatePublished - Apr 1995

Keywords

  • FK506
  • GAP-43
  • axonal transport
  • calcineurin
  • growth-associated proteins
  • immunosuppressants

ASJC Scopus subject areas

  • Neuroscience(all)

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