Abstract
An extensive catalog of plasma membrane (PM) protein mutations related to phenotypic diseases is associated with incorrect protein folding and/or localization. These impairments, in addition to dysfunction, frequently promote protein aggregation, which can be detrimental to cells. Here, we review PM protein processing, from protein synthesis in the endoplasmic reticulum to delivery to the PM, stressing the main repercussions of processing failures and their physiological consequences in pathologies, and we summarize the recent proposed therapeutic strategies to rescue misassembled proteins through different types of chaperones and/or small molecule drugs that safeguard protein quality control and regulate proteostasis.
Highlights
We understand the plasma membrane (PM) not as a simple lipid bilayer protecting the cells or surrounding the cytoplasm but as a collection of stably folded membrane proteins (MPs) in an asymmetric arrangement
We focus on PM proteins, analyzing their synthesis, folding, and trafficking in addition to the mechanism allowing their expression and stability at the membrane, and highlighting approaches by which natural and synthetic chaperones can be used to rescue misfolded phenotypes as strategic therapies to treat misfolding-related diseases
Molecular chaperones are proteins that interact with a nascent protein to assist the stabilization of the native conformation, allowing the protein to remain in the intermediate states for longer during the folding process, but chaperones are frequently absent in the final functional structure [63]
Summary
We understand the plasma membrane (PM) not as a simple lipid bilayer protecting the cells or surrounding the cytoplasm but as a collection of stably folded membrane proteins (MPs) in an asymmetric arrangement. In the PM, peptides interact with the lipid bilayer hydrocarbon core, the bilayer interface, and water in a minimum free energy state, forming complex and dynamic protein–lipid structures that participate directly as messengers or regulators of many signal transduction cascades. Regulation of these complex structures is essential for life and health [1,2,3]. We focus on PM proteins, analyzing their synthesis, folding, and trafficking in addition to the mechanism allowing their expression and stability at the membrane, and highlighting approaches by which natural and synthetic chaperones can be used to rescue misfolded phenotypes as strategic therapies to treat misfolding-related diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
