Protein family FAM241 in human and mouse DOI Creative Commons
Quinlan A. Doctrove, Young Nyun Park, Daniel G. Calame

et al.

Mammalian Genome, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. and FAM241A comprise protein family FAM241 encoding proteins 121 132 amino acid residues, respectively. The exhibit 25% sequence identity contain domain unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates. Phylogenetic comparison indicates duplication the ancestral gene occurred prior to origin fish. has been deleted avian lineage. Fam241a Fam241b are widely expressed mouse tissues. Experimental knockout Fam241a, Fam241b, double knockout, did not generate visible phenotype. Knockout Fam241A Fam241B exacerbate phenotype FIG4 null mice. RNAseq brain RNA mice detected reduced expression several genes including Arke1e1 RnaseL. human variant p.Val115Gly identified patient with developmental delay. Lysosome morphology patient-derived fibroblasts normal. In previous studies, appeared co-localize endoplasmic reticulum. molecular this ancient remains be determined.

Language: Английский

The spectrum of lysosomal stress and damage responses: from mechanosensing to inflammation DOI Creative Commons
Ori Scott, Ekambir Saran, Spencer A. Freeman

et al.

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract Cells and tissues turn over their aged damaged components in order to adapt a changing environment maintain homeostasis. These functions rely on lysosomes, dynamic heterogeneous organelles that play essential roles nutrient redistribution, metabolism, signaling, gene regulation, plasma membrane repair, immunity. Because of metabolic fluctuations pathogenic threats, lysosomes must the short long term functionality. In response such challenges, deploy variety mechanisms prevent breaching escape contents, including pathogen-associated molecules hydrolases. While transient permeabilization lysosomal can have acute beneficial effects, supporting inflammation antigen cross-presentation, sustained or repeated perforations adverse transcriptional consequences lead cell death. This review outlines factors contributing stress damage perception, as well remedial processes aimed at addressing disruptions. We conclude plays widespread human physiology pathology, understanding manipulation which open door novel therapeutic strategies.

Language: Английский

Citations

0
PIKFYVE inhibition induces endosome- and lysosome-derived vacuole enlargement via ammonium accumulation DOI Creative Commons
Junsuke Uwada,

Hitomi Nakazawa,

Takeshi Kiyoi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 20, 2024

Abstract FYVE-type zinc finger-containing phosphoinositide kinase (PIKFYVE), that is essential for PtdIns(3,5)P 2 production, an important regulator of lysosomal homeostasis. PIKFYVE dysfunction leads to cytoplasmic vacuolization; however, the underlying mechanism remains unknown. In this study, we explored cause vacuole enlargement upon inhibition in DU145 prostate cancer cells. Enlargement vacuoles by required glutamine and its metabolism glutaminases. Addition ammonia, a metabolite glutamine, was sufficient enlarge via inhibition. Moreover, led intracellular ammonium accumulation. Endosome–lysosome permeabilization resulted leakage from cells, indicating accumulation endosomes lysosomes. Ammonium expansion were suppressed lumen neutralization. It therefore assumed interferes with efflux NH 4 + , which protonated 3 lumen, leading osmotic swelling vacuoles. Notably, or inhibition-induced suppression function autophagic flux. conclusion, study showed PIKfyve disrupts homeostasis Summary statement Inhibition results endosome/lysosome impaired function. This glutamine-derived these events.

Language: Английский

Citations

1
Table of Contents DOI Open Access
W Feero, Robert D. Steiner, Anne Slavotinek

et al.

Genetics in Medicine, Journal Year: 2024, Volume and Issue: 26(5), P. 101133 - 101133

Published: May 1, 2024

Language: Английский

Citations

0
SLC12A9 is an immunological and prognostic biomarker for glioma DOI
Danting Li, Peilin Zheng, Shoujun Huang

et al.

Gene, Journal Year: 2024, Volume and Issue: unknown, P. 149136 - 149136

Published: Nov. 1, 2024

Language: Английский

Citations

0
Protein family FAM241 in human and mouse DOI Creative Commons
Quinlan A. Doctrove, Young Nyun Park, Daniel G. Calame

et al.

Mammalian Genome, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. and FAM241A comprise protein family FAM241 encoding proteins 121 132 amino acid residues, respectively. The exhibit 25% sequence identity contain domain unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates. Phylogenetic comparison indicates duplication the ancestral gene occurred prior to origin fish. has been deleted avian lineage. Fam241a Fam241b are widely expressed mouse tissues. Experimental knockout Fam241a, Fam241b, double knockout, did not generate visible phenotype. Knockout Fam241A Fam241B exacerbate phenotype FIG4 null mice. RNAseq brain RNA mice detected reduced expression several genes including Arke1e1 RnaseL. human variant p.Val115Gly identified patient with developmental delay. Lysosome morphology patient-derived fibroblasts normal. In previous studies, appeared co-localize endoplasmic reticulum. molecular this ancient remains be determined.

Language: Английский

Citations

0