Dépôt numérique

CLN5 and CLN3 function as a complex to regulate endolysosome function

Yasa, Seda; Sauvageau, Etienne; Modica, Graziana et Lefrancois, Stephane ORCID logoORCID: https://orcid.org/0000-0002-3312-9594 (2021). CLN5 and CLN3 function as a complex to regulate endolysosome function Biochemical Journal , vol. 478 , nº 12. pp. 2339-2357. DOI: 10.1042/bcj20210171.

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CLN5 is a soluble endolysosomal protein whose function is poorly understood. Mutations in this protein cause a rare neurodegenerative disease, Neuronal Ceroid Lipofuscinosis. We previously found that depletion of CLN5 leads to dysfunctional retromer, resulting in the degradation of the lysosomal sorting receptor, sortilin. However, how a soluble lysosomal protein can modulate the function of a cytosolic protein, retromer, is not known. In this work, we show that deletion of CLN5 not only results in retromer dysfunction, but also in impaired endolysosome fusion events. This results in delayed degradation of endocytic proteins and in defective autophagy. CLN5 modulates these various pathways by regulating downstream interactions between CLN3, an endolysosomal integral membrane protein whose mutations also result in Neuronal Ceroid Lipofuscinosis, RAB7A, and a subset of RAB7A effectors. Our data supports a model where CLN3 and CLN5 function as an endolysosomal complex regulating various functions.

Type de document: Article
Mots-clés libres: CLN3; CLN5; RAB7A; Endosomes; Palmitoylation; Retromer
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 23 juin 2022 02:48
Dernière modification: 23 juin 2022 02:48
URI: https://espace.inrs.ca/id/eprint/12464

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