Show simple item record

dc.contributor.authorD'Atri, I
dc.contributor.authorMartin, E-R
dc.contributor.authorYang, L
dc.contributor.authorSears, E
dc.contributor.authorBaple, E
dc.contributor.authorCrosby, AH
dc.contributor.authorChilton, JK
dc.contributor.authorOguro-Ando, A
dc.date.accessioned2024-04-25T13:27:22Z
dc.date.available2024-04-25T13:27:22Z
dc.date.issued2024-05-01
dc.identifier.issn0304-3940
dc.identifier.issn1872-7972
dc.identifier.other137778
dc.identifier.urihttps://pearl.plymouth.ac.uk/handle/10026.1/22321
dc.description.abstract

The endoplasmic reticulum (ER) plays an indispensable role in cellular processes, including maintenance of calcium homeostasis, and protein folding, synthesized and processing. Disruptions in these processes leading to ER stress and the accumulation of misfolded proteins can instigate the unfolded protein response (UPR), culminating in either restoration of balanced proteostasis or apoptosis. A key player in this intricate balance is CLCC1, an ER-resident chloride channel, whose essential role extends to retinal development, regulation of ER stress, and UPR. The importance of CLCC1 is further underscored by its interaction with proteins localized to mitochondria-associated endoplasmic reticulum membranes (MAMs), where it participates in UPR induction by MAM proteins. In previous research, we identified a p.(Asp25Glu) pathogenic CLCC1 variant associated with retinitis pigmentosa (RP) (CLCC1 hg38 NC_000001.11; NM_001048210.3, c.75C > A; UniprotKB Q96S66). In attempt to decipher the impact of this variant function, we leveraged liquid chromatography-mass spectrometry (LC-MS) to identify likely CLCC1-interacting proteins. We discovered that the CLCC1 interactome is substantially composed of proteins that localize to ER compartments and that the Asp25Glu variant results in noticeable loss and gain of specific protein interactors. Intriguingly, the analysis suggests that the CLCC1Asp25Glu mutant protein exhibits a propensity for increased interactions with cytoplasmic proteins compared to its wild-type counterpart. To corroborate our LC-MS data, we further scrutinized two novel CLCC1 interactors, Calnexin and SigmaR1, chaperone proteins that localize to the ER and MAMs. Through microscopy, we demonstrate that CLCC1 co-localizes with both proteins, thereby validating our initial findings. Moreover, our results reveal that CLCC1 co-localizes with SigmaR1 not merely at the ER, but also at MAMs. These findings reinforce the notion of CLCC1 interacting with MAM proteins at the ER-mitochondria interface, setting the stage for further exploration into how these interactions impact ER or mitochondria function and lead to retinal degenerative disease when impaired.

dc.format.extent137778-137778
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.subjectCLCC1
dc.subjectEndoplasmic reticulum
dc.subjectMAM
dc.subjectRetinitis pigmentosa
dc.subjectSigmaR1
dc.titleUnraveling the CLCC1 interactome: Impact of the Asp25Glu variant and its interaction with SigmaR1 at the Mitochondrial-Associated ER Membrane (MAM).
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
dc.typeResearch Support, N.I.H., Extramural
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/38621504
plymouth.volume830
plymouth.publisher-urlhttp://dx.doi.org/10.1016/j.neulet.2024.137778
plymouth.publication-statusPublished
plymouth.journalNeurosci Lett
dc.identifier.doi10.1016/j.neulet.2024.137778
plymouth.organisational-group|Plymouth
plymouth.organisational-group|Plymouth|Faculty of Health
plymouth.organisational-group|Plymouth|REF 2021 Researchers by UoA
plymouth.organisational-group|Plymouth|Users by role
plymouth.organisational-group|Plymouth|Users by role|Current Academic staff
plymouth.organisational-group|Plymouth|REF 2021 Researchers by UoA|UoA01 Clinical Medicine
plymouth.organisational-group|Plymouth|Faculty of Health|Peninsula Medical School
dc.publisher.placeIreland
dcterms.dateAccepted2024-04-12
dc.date.updated2024-04-25T13:27:20Z
dc.rights.embargodate2024-4-27
dc.identifier.eissn1872-7972
rioxxterms.versionofrecord10.1016/j.neulet.2024.137778


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record


All items in PEARL are protected by copyright law.
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author.
Theme by 
Atmire NV