Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy.

ABSTRACT: Peripheral Myelin Protein 22 (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 a

SUBMITTER: Pashkova N 

PROVIDER: S-EPMC11700639 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature