Efficient Cargo Sorting by ESCRT-I and the Subsequent Release of ESCRT-I from Multivesicular Bodies Requires the Subunit Mvb12

Curtiss, Matt; Jones, Charles B.; Babst, Markus

doi:10.1091/mbc.e06-07-0588

Cited by 63 publications

(67 citation statements)

References 43 publications

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“…This cluster, which contains 18 genes that encode all 13 nonredundant V-ATPase subunits, 2 overlapping ORFs, and 3 dedicated V-ATPase assembly factors, lacks only VPH1 and STV1, which encode two isoforms of the 100-kDa stator subunit with partially overlapping functions. The secondlargest cluster contains 13 genes corresponding to all known components of ESCRT-I, -II, and -III complexes apart from the newly described ESCRT-I subunit Mvb12 (Chu et al, 2006;Curtiss et al, 2007;Kostelansky et al, 2007;Oestreich et al, 2007) and also includes the ESCRT-associated factors Vps27p, Vps4p, and Bro1p (Bowers and Stevens, 2005). The fact that all three ESCRT subcomplexes were found in a single cluster is consistent with their highly interdependent function in MVB formation.…”

Section: Identification Of New and Known Complexesmentioning

confidence: 52%

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Schluter

Lam

Brumm

et al. 2008

MBoC

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Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors. This technique effectively identifies components of known and novel protein assemblies. We report the characterization of a previously undescribed endosome sorting complex that contains two well-conserved proteins with four predicted membrane-spanning domains. Vps55p and Vps68p form a complex that acts with or downstream of ESCRT function to regulate endosomal trafficking. Loss of Vps68p disrupts recycling to the TGN as well as onward trafficking to the vacuole without preventing the formation of lumenal vesicles within the MVB. Our results suggest the Vps55/68 complex mediates a novel, conserved step in the endosomal maturation process. INTRODUCTIONEndosomal protein sorting is a highly conserved cellular process that is required for receptor down-regulation, viral replication, and development (Katzmann et al., 2002;Morita and Sundquist, 2004). Much progress has been made in recent years in identifying distinct multiprotein complexes that regulate the fusion of primary endocytic vesicles, the maturation of an early endosome into a multivesicular body (MVB), and the recycling of proteins and lipids to other organelles (Gruenberg and Stenmark, 2004;Bonifacino and Rojas, 2006). The ESCRT-I, -II, and -III complexes (endosomal-sorting complex required for transport), which act in sequence to regulate the formation of internal vesicles at the MVB, play a central role in endosome biogenesis (Katzmann et al., 2002;Hurley and Emr, 2006). Other transport complexes regulate the targeting and fusion of endosomes or endosome-derived vesicles with other organelles (Bowers and Stevens, 2005;Bonifacino and Rojas, 2006).Many components of the endosomal-sorting machinery were first identified in yeast genetic screens for mutants that are defective in protein transport to the yeast vacuole, which requires functional endosomal sorting and recycling (Bowers and Stevens, 2005). Most of these components have a conserved role in endosome biogenesis in higher cells. Mammalian homologues have been identified for most if not all yeast ESCRT subunits (von Schwedler et al., 2003;Hurley and Emr, 2006), and at least some of the machinery that regulates recycling from the MVB is also well conserved. For example, the five-subunit retromer complex that mediates endosome-to-trans-Golgi network (TGN) transport in yeast is associated with tubular regions of the endosome in mammalian cells and mediates retrograde transport (Arighi et al., 2004;Seaman, 2004). In the past 20 years, classical genetic screens have identified more than 50 vacuole protein-sorting (VPS) genes (Bowers and Stevens, 2005). Surprisingly, ...

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Section: Identification Of New and Known Complexesmentioning

confidence: 52%

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Schluter

Lam

Brumm

et al. 2008

MBoC

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“…Fluorescence microscopy was performed on a deconvolution microscope (DeltaVision, Applied Precision, Issaquah, WA). Sephacryl S300 (16/60 column, GE Healthcare, Waukesha, WI) gel filtration analysis of yeast cell extract was performed as described in Curtiss et al (2007). Superose 6 (3.2/30 column, GE Healthcare) gel filtration analysis of purified proteins was performed in presence of 1 mM ATP, 150 mM KAc, 20 mM HEPES, pH 7.4, and 5 mM MgAc 2 at a flow rate of 40 l/min.…”

Section: Methodsmentioning

confidence: 99%

Ist1 Regulates Vps4 Localization and Assembly

Dimaano

Jones

Hanono

et al. 2008

MBoC

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123

192

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The ESCRT protein complexes are recruited from the cytoplasm and assemble on the endosomal membrane into a protein network that functions in sorting of ubiquitinated transmembrane proteins into the multivesicular body (MVB) pathway. This transport pathway packages cargo proteins into vesicles that bud from the MVB limiting membrane into the lumen of the compartment and delivers these vesicles to the lysosome/vacuole for degradation. The dissociation of ESCRT machinery by the AAA-type ATPase Vps4 is a necessary late step in the formation of MVB vesicles. This ATP-consuming step is regulated by several Vps4-interacting proteins, including the newly identified regulator Ist1. Our data suggest that Ist1 has a dual role in the regulation of Vps4 activity: it localizes to the ESCRT machinery via Did2 where it positively regulates recruitment of Vps4 and it negatively regulates Vps4 by forming an Ist1-Vps4 heterodimer, in which Vps4 cannot bind to the ESCRT machinery. The activity of the MVB pathway might be in part determined by outcome of these two competing activities.

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“…However, loss of ESCRT-I does not prevent ESCRT-II association with endosomes, although it does hamper ESCRT-III recruitment (Babst et al 2002b). Loss of ESCRT-0 does not block the association of ESCRT-III with endosomes (Curtiss et al 2007), and loss of ESCRT-I inhibits the recruitment of clathrin to Hrs-positive endosomes (Doyotte et al 2005). Although the presence of Vps27 (ESCRT-0) is required for the association of ESCRT-I with membranes, mutating the motifs in Vps27 that bind Vps23 (ESCRT-I) does not alter MVB formation and only partially affects the sorting efficiency of particular cargo (Bilodeau et al 2003).…”

Section: Protein Machinerymentioning

confidence: 99%

Biogenesis and Function of Multivesicular Bodies

Piper

Katzmann

2007

Annu. Rev. Cell Dev. Biol.

658

660

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The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.

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Efficient Cargo Sorting by ESCRT-I and the Subsequent Release of ESCRT-I from Multivesicular Bodies Requires the Subunit Mvb12

Cited by 63 publications

References 43 publications

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Ist1 Regulates Vps4 Localization and Assembly

Biogenesis and Function of Multivesicular Bodies

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