Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast multivesicular body

Lottridge, Jillian; Flannery, Andrew R.; Vincelli, Jennifer L.; Stevens, Tom H.

doi:10.1073/pnas.0601712103

Cited by 80 publications

(129 citation statements)

References 32 publications

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“…As will be described below, we confirmed in parallel studies that LIP5 also binds to CHMP5 with comparable or even higher affinity (see Figure 8). The interaction of LIP5 with CHMP1B might have been anticipated based on earlier studies in yeast (Lottridge et al, 2006), but the association of LIP5 with the core ESCRT-III proteins CHMP2A and CHMP3 was unexpected and raises the possibility of a more intimate relationship between LIP5 and ESCRT-III than previously appreciated.…”

Section: Interactions Between Lip5 and Escrt-iii Proteinsmentioning

confidence: 71%

“…A previous study demonstrated that LIP5 bound efficiently but apparently uniquely to the ESCRT-III like protein CHMP5 (Ward et al, 2005); this interaction was also found in a reciprocal immunoprecipitation of proteins that bind to CHMP5 (Ma et al, 2007). In yeast, Vta1p, the LIP5 orthologue, binds both to Vps60p (CHMP5 ortholog; Shiflett et al, 2004;Azmi et al, 2006;Rue et al, 2007) and to Did2p/Vps46p (CHMP1 ortholog; Lottridge et al, 2006). On this basis, we asked whether LIP5 also interacts with other human ESCRT-III proteins.…”

Section: Lip5 Binds Tightly To Several Escrt-iii Proteins In Additionmentioning

confidence: 99%

“…Less well explored connections between Vta1 and a few other ESCRT-III-related proteins have been reported, primarily in yeast. In particular, Vta1 binds to Did2/Vps46 (yeast ortholog of CHMP1; Lottridge et al, 2006) and the name Vta1 (Vps twenty [Vps20]-associated 1) was originally derived from a connection between Vps20 and Vta1, although this interaction has not been reproduced (Yeo et al, 2003;Azmi et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly

Shim

Merrill

Hanson

2008

MBoC

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The AAA؉ ATPase VPS4 plays an essential role in multivesicular body biogenesis and is thought to act by disassembling ESCRT-III complexes. VPS4 oligomerization and ATPase activity are promoted by binding to LIP5. LIP5 also binds to the ESCRT-III like protein CHMP5/hVps60, but how this affects its function remains unclear. Here we confirm that LIP5 binds tightly to CHMP5, but also find that it binds well to additional ESCRT-III proteins including CHMP1B, CHMP2A/ hVps2-1, and CHMP3/hVps24 but not CHMP4A/hSnf7-1 or CHMP6/hVps20. LIP5 binds to a different region within CHMP5 than within the other ESCRT-III proteins. In CHMP1B and CHMP2A, its binding site encompasses sequences at the proteins' extreme C-termini that overlap with "MIT interacting motifs" (MIMs) known to bind to VPS4. We find unexpected evidence of a second conserved binding site for VPS4 in CHMP2A and CHMP1B, suggesting that LIP5 and VPS4 may bind simultaneously to these proteins despite the overlap in their primary binding sites. Finally, LIP5 binds preferentially to soluble CHMP5 but instead to polymerized CHMP2A, suggesting that the newly defined interactions between LIP5 and ESCRT-III proteins may be regulated by ESCRT-III conformation. These studies point to a role for direct binding between LIP5 and ESCRT-III proteins that is likely to complement LIP5's previously described ability to regulate VPS4 activity.

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Section: Interactions Between Lip5 and Escrt-iii Proteinsmentioning

confidence: 71%

Section: Lip5 Binds Tightly To Several Escrt-iii Proteins In Additionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly

Shim

Merrill

Hanson

2008

MBoC

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“…Vta1 stimulation of Vps4 occurs through both the Vta1 VSL domain and the neighboring VSE (31,53). The VSL domain binds to the Vps4 ␤-domain to promote oligomerization and stimulate ATP hydrolysis (39,40,41,43,55). An additional level of Vps4 stimulation is mediated by the VSE, and the VSE is also required for the enhanced stimulation that occurs when ESCRT-III subunits bind to the amino-terminal MIT domains of Vta1 (53).…”

Section: Discussionmentioning

confidence: 99%

Vps4 Stimulatory Element of the Cofactor Vta1 Contacts the ATPase Vps4 α7 and α9 to Stimulate ATP Hydrolysis

Davies

Norgan

Payne

et al. 2014

Journal of Biological Chemistry

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Background: ESCRT-III can enhance Vta1 stimulation of Vps4 ATPase activity via the Vps4 stimulatory element (VSE) of Vta1. Results: ␣7 and ␣9 of the Vps4 small AAA domain mediate VSE stimulation, contributing to Vps4 function in vivo. Conclusion: Vta1 contacts Vps4 ␣7 and ␣9 during ESCRT-III-enhanced stimulation of Vps4. Significance: These studies identify a novel mechanism of Vps4 stimulation.

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“…We found that mutation of either VPS68 or VPS55 similarly slows the transit of biosynthetic and endocytic cargo proteins through the MVB, but does not block the formation of intralumenal vesicles or cause the accumulation of an aberrant protease-active compartment. A subset of class E vps mutants (including did2/fti1/vps46, vps60, and vta1) that affect ESCRT function by regulating the AAA ATPase Vps4p exhibit mild CPY-sorting defects (Ͻ20%) and partial impairment of lumenal MVB vesicle formation (Azmi et al, 2006;Lottridge et al, 2006). Our results do not preclude a similar role for the Vps55/68 complex in regulating ESCRT proteins and increasing the efficiency of lumenal vesicle formation; however, the strong CPY-sorting defects of vps55 and vps68 mutants suggest they have a different function.…”

Section: The Vps55/68 Complex Is Required For Two Transport Steps Outmentioning

confidence: 99%

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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Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast multivesicular body

Abstract: endosome ͉ ESCRT complexes ͉ protein sorting ͉ Vps ͉ class E

Cited by 80 publications

References 32 publications

Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly

Novel Interactions of ESCRT-III with LIP5 and VPS4 and their Implications for ESCRT-III Disassembly

Vps4 Stimulatory Element of the Cofactor Vta1 Contacts the ATPase Vps4 α7 and α9 to Stimulate ATP Hydrolysis

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

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