Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening

Sangwoo Shim, Joseph P. Yuan, Ju Young Kim, Weizhong Zeng, Guo Huang, Aleksandr Milshteyn, Dorothee Kern, Shmuel Muallem, Guo li Ming, Paul F Worley

Research output: Contribution to journalArticle

Abstract

Immunophilins, including FK506-binding proteins (FKBPs), are protein chaperones with peptidyl-prolyl isomerase (PPIase) activity. Initially identified as pharmacological receptors for immunosuppressants to regulate immune responses via isomerase-independent mechanisms, FKBPs are most highly expressed in the nervous system, where their physiological function as isomerases remains unknown. We demonstrate that FKBP12 and FKBP52 catalyze cis/trans isomerization of regions of TRPC1 implicated in controlling channel opening. FKBP52 mediates stimulus-dependent TRPC1 gating through isomerization, which is required for chemotropic turning of neuronal growth cones to netrin-1 and myelin-associated glycoprotein and for netrin-1/DCC-dependent midline axon guidance of commissural interneurons in the developing spinal cord. By contrast, FKBP12 mediates spontaneous opening of TRPC1 through isomerization and is not required for growth cone responses to netrin-1. Our study demonstrates a novel physiological function of proline isomerases in chemotropic nerve guidance through TRPC1 gating and may have significant implication in clinical applications of immunophilin-related therapeutic drugs.

Original languageEnglish (US)
Pages (from-to)471-483
Number of pages13
JournalNeuron
Volume64
Issue number4
DOIs
StatePublished - Nov 25 2009

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Peptidylprolyl Isomerase
Growth Cones
Tacrolimus Binding Protein 1A
Immunophilins
Tacrolimus Binding Proteins
Isomerases
Myelin-Associated Glycoprotein
Immunosuppressive Agents
Nervous System
Spinal Cord
Pharmacology
Pharmaceutical Preparations
netrin-1
Axon Guidance
tacrolimus binding protein 4
Proteins
Therapeutics

Keywords

  • CELLBIO
  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening. / Shim, Sangwoo; Yuan, Joseph P.; Kim, Ju Young; Zeng, Weizhong; Huang, Guo; Milshteyn, Aleksandr; Kern, Dorothee; Muallem, Shmuel; Ming, Guo li; Worley, Paul F.

In: Neuron, Vol. 64, No. 4, 25.11.2009, p. 471-483.

Research output: Contribution to journalArticle

Shim, S, Yuan, JP, Kim, JY, Zeng, W, Huang, G, Milshteyn, A, Kern, D, Muallem, S, Ming, GL & Worley, PF 2009, 'Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening', Neuron, vol. 64, no. 4, pp. 471-483. https://doi.org/10.1016/j.neuron.2009.09.025
Shim, Sangwoo ; Yuan, Joseph P. ; Kim, Ju Young ; Zeng, Weizhong ; Huang, Guo ; Milshteyn, Aleksandr ; Kern, Dorothee ; Muallem, Shmuel ; Ming, Guo li ; Worley, Paul F. / Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening. In: Neuron. 2009 ; Vol. 64, No. 4. pp. 471-483.
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