Journal article
Mutations in the cytoplasmic domain of P0 reveal a role for PKC-mediated phosphorylation in adhesion and myelination
The Journal of cell biology, Vol.155(3), pp.439-446
10/29/2001
DOI: 10.1083/jcb.200107114
PMCID: PMC2150845
PMID: 11673479
Abstract
Mutations in P0 (MPZ), the major myelin protein of the peripheral nervous system, cause the inherited demyelinating neuropathy Charcot-Marie-Tooth disease type 1B. P0 is a member of the immunoglobulin superfamily and functions as a homophilic adhesion molecule. We now show that point mutations in the cytoplasmic domain that modify a PKC target motif (RSTK) or an adjacent serine residue abolish P0 adhesion function and can cause peripheral neuropathy in humans. Consistent with these data, PKCα along with the PKC binding protein RACK1 are immunoprecipitated with wild-type P0, and inhibition of PKC activity abolishes P0-mediated adhesion. Point mutations in the RSTK target site that abolish adhesion do not alter the association of PKC with P0; however, deletion of a 14 amino acid region, which includes the RSTK motif, does abolish the association. Thus, the interaction of PKCα with the cytoplasmic domain of P0 is independent of specific target residues but is dependent on a nearby sequence. We conclude that PKC-mediated phosphorylation of specific residues within the cytoplasmic domain of P0 is necessary for P0-mediated adhesion, and alteration of this process can cause demyelinating neuropathy in humans.
Details
- Title: Subtitle
- Mutations in the cytoplasmic domain of P0 reveal a role for PKC-mediated phosphorylation in adhesion and myelination
- Creators
- Wenbo Xu - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University Detroit, MI 48202Michael Shy - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University Detroit, MI 48202John Kamholz - Department of Neurology and the Center for Molecular Medicine and Genetics, Wayne State University Detroit, MI 48202Lisa Elferink - Biomedical Marine Institute and Department of Biophysics and Physiology, Galveston, TX 77555Gang Xu - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242Jack Lilien - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242Janne Balsamo - Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.155(3), pp.439-446
- DOI
- 10.1083/jcb.200107114
- PMID
- 11673479
- PMCID
- PMC2150845
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 10/29/2001
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984020898902771
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