Overloaded Endoplasmic Reticulum–Golgi Compartments, a Possible Pathomechanism of Peripheral Neuropathies Caused by Mutations of the Peripheral Myelin Protein PMP22

摘要: Nonconservative point mutations of the peripheral myelin protein 22 (PMP22) are associated with Charcot-Marie-Tooth type 1A disease, most common inherited neuropathy in humans, and Trembler J (TrJ) (Tr) alleles mice. We investigated intracellular transport wild-type PMP22 its TrJ Tr mutant forms Schwann cells a non-neuronal cell line. In contrast to wild type, proteins were not inserted into plasma membrane accumulated endoplasmic reticulum Golgi compartments. Coexpression each confirmed different distribution forms, indicating that neither nor has dominant-negative effect on cellular PMP22. Accumulation immunoreactivity body myelinating was also observed nerve biopsies obtained from CMT1A patients carrying mutation. propose impaired trafficking mutated affects physiology leading instability loss.