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Shim, J. H. et al. CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis. J. Cell Biol. 172, 1045-1056

Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 04/2006; 172(7):1045-56. DOI: 10.1083/jcb.200509041
Source: PubMed

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 traffic 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.

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    • "Endocytic downregulation of cell surface receptors is thought to be a key regulatory step in establishing the appropriate extent of signaling. Indeed, disruption of late endosome/multivesicular body (MVB) function by small interfering RNA (siRNA)-mediated suppression of Chmp5, a subunit of the MVB-forming complex, i.e., endosomal sorting complex required for transport III (ESCRT-III), results in defective silencing of RTKs and TGF-b signaling (Shim et al., 2006 "
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    Developmental Cell 06/2012; 22(6):1163-75. DOI:10.1016/j.devcel.2012.05.009 · 10.37 Impact Factor
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    • "Both CHMP5 and CHMP4B C - Terminal Tails Bind Brox Structure 20 , 887 – 898 , May 9 , 2012 ª2012 Elsevier Ltd All rights reserved 893 accumulation of late endosome compartments , and enhanced cell surface receptor signaling due to diminished receptor turn - over , and was embryonically lethal ( Shim et al . , 2006 ) . In addi - tion , CHMP5 was shown to be essential for spindle formation during mitosis and was found to localize at the midbody during cytokinesis , suggesting its broad participation in cell division ( Morita et al . , 2010 , 2007 ) . Furthermore , CHMP5 was reported to play a key role in the initiation of innate immune response aga"
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    Structure 04/2012; 20(5):887-98. DOI:10.1016/j.str.2012.03.001 · 6.79 Impact Factor
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    • "In Drosophila, mutation of the ESCRT-0 subunit Hrs impedes downregulation of the EGFR, PVR (PDGFR and VEGFR-related), and Torso RTKs (Jekely and Rorth, 2003; Lloyd et al., 2002), as well as the non-RTK receptors Notch (Herz et al., 2006; Jekely and Rorth, 2003; Thompson et al., 2005; Vaccari and Bilder, 2005), Hedgehog receptor (Jekely and Rorth, 2003), and Dpp (TGF-β-related) receptor (Jekely and Rorth, 2003). The TGF-β receptor is an ESCRT substrate in human cells (Shim et al., 2006). A role for ESCRT-0 in downregulating E-cadherin has been proposed (Toyoshima et al., 2007). "
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