Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

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 biosy...

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Autores: Xu, Haijin, Isenmann, Sandra, López Hernández, Tania, Estévez Povedano, Raúl, Lukacs, Gergely L., Apaja, Pirjo M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/180331
Acceso en línea:https://hdl.handle.net/2445/180331
Access Level:acceso abierto
Palabra clave:Homeòstasi
Neuròglia
Homeostasis
Neuroglia
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spelling Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locationsXu, HaijinIsenmann, SandraLópez Hernández, TaniaEstévez Povedano, RaúlLukacs, Gergely L.Apaja, Pirjo M.HomeòstasiNeurògliaHomeostasisNeurogliaThe 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.Springer Science and Business Media LLC2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/180331Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-021-97777-4Scientific Reports, 2021, vol. 11, num. 1https://doi.org/10.1038/s41598-021-97777-4cc by (c) Xu, Haijin et al, 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1803312026-05-27T06:46:51Z
dc.title.none.fl_str_mv Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
title Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
spellingShingle Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
Xu, Haijin
Homeòstasi
Neuròglia
Homeostasis
Neuroglia
title_short Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
title_full Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
title_fullStr Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
title_full_unstemmed Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
title_sort Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
dc.creator.none.fl_str_mv Xu, Haijin
Isenmann, Sandra
López Hernández, Tania
Estévez Povedano, Raúl
Lukacs, Gergely L.
Apaja, Pirjo M.
author Xu, Haijin
author_facet Xu, Haijin
Isenmann, Sandra
López Hernández, Tania
Estévez Povedano, Raúl
Lukacs, Gergely L.
Apaja, Pirjo M.
author_role author
author2 Isenmann, Sandra
López Hernández, Tania
Estévez Povedano, Raúl
Lukacs, Gergely L.
Apaja, Pirjo M.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Homeòstasi
Neuròglia
Homeostasis
Neuroglia
topic Homeòstasi
Neuròglia
Homeostasis
Neuroglia
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/180331
url https://hdl.handle.net/2445/180331
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-97777-4
Scientific Reports, 2021, vol. 11, num. 1
https://doi.org/10.1038/s41598-021-97777-4
dc.rights.none.fl_str_mv cc by (c) Xu, Haijin et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Xu, Haijin et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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