Back to Search
Start Over
PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome
- Source :
- Nature communications. 1
- Publication Year :
- 2010
-
Abstract
- Membrane fusion and fission events in intracellular trafficking are controlled by both intraluminal Ca(2+) release and phosphoinositide (PIP) signalling. However, the molecular identities of the Ca(2+) release channels and the target proteins of PIPs are elusive. In this paper, by direct patch-clamping of the endolysosomal membrane, we report that PI(3,5)P(2), an endolysosome-specific PIP, binds and activates endolysosome-localized mucolipin transient receptor potential (TRPML) channels with specificity and potency. Both PI(3,5)P(2)-deficient cells and cells that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking defects in the late endocytic pathway. We find that the enlarged vacuole phenotype observed in PI(3,5)P(2)-deficient mouse fibroblasts is suppressed by overexpression of TRPML1. Notably, this PI(3,5)P(2)-dependent regulation of TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces Ca(2+) release from the vacuole. In this study, we show that this release requires both PI(3,5)P(2) production and a yeast functional TRPML homologue. We propose that TRPMLs regulate membrane trafficking by transducing information regarding PI(3,5)P(2) levels into changes in juxtaorganellar Ca(2+), thereby triggering membrane fusion/fission events.
- Subjects :
- Phosphatidylinositol 3,5-bisphosphate
TRPML
Biophysics
General Physics and Astronomy
TRPM Cation Channels
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Cell membrane
Transient receptor potential channel
chemistry.chemical_compound
Mice
Transient Receptor Potential Channels
Phosphatidylinositol Phosphates
medicine
Animals
Ion channel
Multidisciplinary
Cell Membrane
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Biological Transport
General Chemistry
Endolysosome
Cell biology
Electrophysiology
medicine.anatomical_structure
Two-pore channel
chemistry
Lysosomes
Protein Binding
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....3498e74a49ef6139e524021a4d2cb886