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http://hdl.handle.net/2445/180331
Title: | Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations |
Author: | Xu, Haijin Isenmann, Sandra López Hernández, Tania Estévez, Raúl Lukacs, Gergely L. Apaja, Pirjo M. |
Keywords: | Homeòstasi Neuròglia Homeostasis Neuroglia |
Issue Date: | 16-Sep-2021 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | The significance of crosstalks among constituents of plasma membrane protein clusters/complexes in cellular proteostasis and protein quality control (PQC) remains incompletely understood. Examining the glial (enriched) cell adhesion molecule (CAM), we demonstrate its chaperone-like role in the biosynthetic processing of the megalencephalic leukoencephalopathy with subcortical cyst 1 (MLC1)-heteromeric regulatory membrane protein complex, as well as the function of the GlialCAM/MLC1 signalling complex. We show that in the absence of GlialCAM, newly synthesized MLC1 molecules remain unfolded and are susceptible to polyubiquitination-dependent proteasomal degradation at the endoplasmic reticulum. At the plasma membrane, GlialCAM regulates the diffusional partitioning and endocytic dynamics of cluster members, including the ClC-2 chloride channel and MLC1. Impaired folding and/or expression of GlialCAM or MLC1 in the presence of diseases causing mutations, as well as plasma membrane tethering compromise the functional expression of the cluster, leading to compromised endo-lysosomal organellar identity. In addition, the enlarged endo-lysosomal compartments display accelerated acidification, ubiquitinated cargo-sorting and impaired endosomal recycling. Jointly, these observations indicate an essential and previously unrecognized role for CAM, where GliaCAM functions as a PQC factor for the MLC1 signalling complex biogenesis and possess a permissive role in the membrane dynamic and cargo sorting functions with implications in modulations of receptor signalling. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-97777-4 |
It is part of: | Scientific Reports, 2021, vol. 11, num. 1 |
URI: | http://hdl.handle.net/2445/180331 |
Related resource: | https://doi.org/10.1038/s41598-021-97777-4 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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41598_2021_Article_97777.pdf | 9.37 MB | Adobe PDF | View/Open |
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