Dataset
PMP22 associates with MPZ
figshare
08/28/2024
DOI: 10.6084/m9.figshare.26219009
Abstract
PMP22 and MPZ are abundant myelin membrane proteins in Schwann cells. The MPZ adhesion protein holds myelin wraps together across the intraperiod line. PMP22 is a tetraspan protein belonging to the Claudin superfamily. Loss of either MPZ or PMP22 causes severe demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy, and duplication of PMP22 causes the most common form of CMT, CMT1A. Yet, the molecular functions provided by PMP22 and how its alteration causes CMT are unknown. Here we find MPZ and PMP22 form a specific complex through interfaces within their transmembrane domains. We also find that the PMP22 A67T patient variant that causes a loss-of-function (Hereditary Neuropathy with Pressure Palsies) phenotype maps to this interface, and blocks MPZ association without affecting localization to the plasma membrane or interactions with other proteins. These data define the molecular basis for the MPZ~PMP22 interaction and indicate this complex fulfills an important function in myelinating cells.
Details
- Title: Subtitle
- PMP22 associates with MPZ
- Creators
- Robert Piper
- Resource Type
- Dataset
- DOI
- 10.6084/m9.figshare.26219009
- Publisher
- figshare
- Grant note
- Ubiquitin-dependent sorting in endosomes and the TGN - R01GM058202 / National Institute of General Medical Sciences (https://ror.org/04q48ey07) Chemical biology of voltage-gated cation channels - R35GM148239 / National Institute of General Medical Sciences (https://ror.org/04q48ey07) The Inherited Neuropathy Consortium (INC) RDCRC- Overall - U54NS065712 / National Institute of Neurological Disorders and Stroke (https://ror.org/01s5ya894)
- Language
- English
- Date published
- 08/28/2024
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984701758502771
Metrics
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