| Abstract: |
Charged MVB protein 5 (CHMP5) is a coiled coil protein homologous to the yeast Vps60/Mos10 gene and other ESCRT-III complex members, although its precise function in either yeast or mammalian cells is unknown. We deleted the CHMP5 gene in mice, resulting in a phenotype of early embryonic lethality, reflecting defective late endosome function and dysregulation of signal transduction. Chmp5-/- cells exhibit enlarged late endosomal compartments that contain abundant internal vesicles expressing proteins that are characteristic of late endosomes and lysosomes. This is in contrast to ESCRT-III mutants in yeast, which are defective in multivesicular body (MVB) formation. The degradative capacity of Chmp5-/- cells was reduced, and undigested proteins from multiple pathways accumulated in enlarged MVBs that failed to traf. c their cargo to lysosomes. Therefore, CHMP5 regulates late endosome function downstream of MVB formation, and the loss of CHMP5 enhances signal transduction by inhibiting lysosomal degradation of activated receptors. © The Rockefeller University Press. |
| Keywords: |
signal transduction; controlled study; unclassified drug; nonhuman; animal cell; mouse; phenotype; mammalia; animals; mice; mice, knockout; cells, cultured; cell compartmentalization; gene expression; transforming growth factor beta; embryo; protein metabolism; cell line; animal experiment; down-regulation; rna, small interfering; embryo development; transfection; phosphorylation; mice, inbred c57bl; animalia; mice, transgenic; gene expression regulation, developmental; amino acid sequence; molecular sequence data; sequence homology, amino acid; intracellular signaling peptides and proteins; nucleotide sequence; carrier proteins; membrane protein; transforming growth factor beta receptor; receptors, transforming growth factor beta; stem cells; gene control; histocompatibility antigens class ii; endocytosis; nih 3t3 cells; embryonic development; biogenesis; lysosome; lysosomes; endosome; receptor down regulation; endosomes; charged multivesicular body protein 5; activin receptors, type i; horseradish peroxidase
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