Modulation of Lysosomal Cl
GXXXP motif
TRPML1
calcium
chloride
lysosome
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
12 07 2023
12 07 2023
Historique:
received:
20
05
2023
revised:
06
07
2023
accepted:
11
07
2023
medline:
31
7
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
epublish
Résumé
Lysosomes are responsible for protein degradation and clearance in cellular recycling centers. It has been known that the lysosomal chloride level is enriched and involved in the intrinsic lysosomal function. However, the mechanism by which chloride levels can be sensed and that of the chloride-mediated lysosomal function is unknown. In this study, we verified that reduced chloride levels acutely induced lysosomal calcium release through TRPML1 and lysosomal repositioning toward the juxtanuclear region. Functionally, low chloride-induced lysosomal calcium release attenuated cellular migration. In addition, spontaneous exposure to low chloride levels dysregulated lysosomal biogenesis and subsequently induced delayed migration and promoted apoptosis. Two chloride-sensing GXXXP motifs in the TRPML1 were identified. Mutations in the GXXXP motif of TRPML1 did not affect chloride levels, and there were no changes in migratory ability. In this study, we demonstrated that the depletion of chloride induces reformation of the lysosomal calcium pool and subsequently dysregulated cancer progression, which will assist in improving therapeutic strategies for lysosomal accumulation-associated diseases or cancer cell apoptosis.
Identifiants
pubmed: 37508500
pii: cells12141835
doi: 10.3390/cells12141835
pmc: PMC10378694
pii:
doi:
Substances chimiques
Calcium
SY7Q814VUP
Chlorides
0
Transient Receptor Potential Channels
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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