Back to Search
Start Over
The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2016
- Publisher :
- The Rockefeller University Press, 2016.
-
Abstract
- The mechanisms and determinants preserving lysosomal membrane stability are unclear. Here, Li et al. show that the lysosomal membrane protein SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, is a key regulator of lysosome integrity and normal adult lifespan.<br />Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity.
- Subjects :
- 0301 basic medicine
Glycosylation
Hydrolases
medicine.medical_treatment
Green Fluorescent Proteins
Longevity
Motility
Cellular homeostasis
Golgi Apparatus
Endosomes
Endoplasmic Reticulum
Article
03 medical and health sciences
Lysosome
medicine
Autophagy
Animals
Insulin
Insulin-Like Growth Factor I
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Research Articles
biology
Protein Stability
Growth factor
Membrane Proteins
Cell Biology
Intracellular Membranes
biology.organism_classification
Cell biology
030104 developmental biology
medicine.anatomical_structure
Membrane protein
Mutation
Signal transduction
Lysosomes
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 215
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....45d06d21318ca03f83a670a8fb83b9fd