Naturally occurring and tumor-associated variants of RNF167 promote lysosomal exocytosis and plasma membrane resealing.

Autor:	Nair SV; School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Thiruvananthapuram 695551, Kerala, India., Narendradev ND; School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Thiruvananthapuram 695551, Kerala, India., Nambiar RP; School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Thiruvananthapuram 695551, Kerala, India., Kumar R; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, India., Srinivasula SM; School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Thiruvananthapuram 695551, Kerala, India sms@iisertvm.ac.in.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2020 Jun 11; Vol. 133 (11). Date of Electronic Publication: 2020 Jun 11.
DOI:	10.1242/jcs.239335
Abstrakt:	Lysosomal exocytosis and resealing of damaged plasma membrane are essential for cellular homeostasis and tumor invasion. However, very little is known of the molecular machinery that regulates these physiological processes. Moreover, no mutations in any of the known regulators of lysosomal exocytosis in primary tumors of patients have been characterized. Here we demonstrate that RNF167-a, a lysosomal-associated ubiquitin ligase, negatively regulates lysosomal exocytosis by inducing perinuclear clustering of lysosomes. Importantly, we also characterized a set of novel natural mutations in RNF167-a, which are commonly found in diverse tumor types. We found that RNF167-a-K97N mutant, unlike the wild type, localizes in the cytoplasm and does not promote perinuclear lysosomal clustering. Furthermore, cells expressing RNF167-a-K97N exhibit dispersed lysosomes, increased exocytosis and enhanced plasma membrane repair. Interestingly, these functional features of RNF167-a-K97N were shared with a naturally occurring short version of RNF167 (isoform RNF167-b). In brief, the results presented here reveal a novel role of RNF167-a, as well as its natural variants RNF167-a-K97N and RNF167-b, as an upstream regulator of lysosomal exocytosis and plasma membrane resealing. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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