Multivesicular Body Morphogenesis

Hanson, Phyllis I.; Cashikar, Anil G.

doi:10.1146/annurev-cellbio-092910-154152

Cited by 504 publications

(463 citation statements)

References 184 publications

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“…Thus, whereas ESCRT-III proteins are required for membrane scission in eHAV biogenesis, there is as yet no evidence that other ESCRTs play a role in eHAV cargo selection. This contrasts with current paradigms for MVB formation and exosome biogenesis (17,25). HAV may thus usurp only part of, and not the entire, exosome biogenesis pathway to gain egress from infected cells.…”

Section: Discussionmentioning

confidence: 69%

“…Mammalian cells shed a variety of types of extracellular vesicles that are highly heterogeneous in size, density, and protein and nucleic acid composition and differ in their mechanisms of biogenesis (9,17). The term "exosome" is generally used to describe a specific subset of these extracellular vesicles that are ∼40 to 150 nm in diameter and formed by inward budding of endosomal membranes in an ESCRT-dependent process that results in MVBs containing multiple intraluminal vesicles (hence the alternative term "multivesicular endosomes") (17,25). MVBs generally transport their cargo to lysosomes for destruction, but some MVBs disgorge their intraluminal vesicles as exosomes following fusion with the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

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Protein composition of the hepatitis A virus quasi-envelope

McKnight

Xie

González‐López

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

124

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The Picornaviridae are a diverse family of RNA viruses including many pathogens of medical and veterinary importance. Classically considered "nonenveloped," recent studies show that some picornaviruses, notably hepatitis A virus (HAV; genus Hepatovirus) and some members of the Enterovirus genus, are released from cells nonlytically in membranous vesicles. To better understand the biogenesis of quasienveloped HAV (eHAV) virions, we conducted a quantitative proteomics analysis of eHAV purified from cell-culture supernatant fluids by isopycnic ultracentrifugation. Amino acid-coded mass tagging (AACT) with stable isotopes followed by tandem mass spectrometry sequencing and AACT quantitation of peptides provided unambiguous identification of proteins associated with eHAV versus unrelated extracellular vesicles with similar buoyant density. Multiple peptides were identified from HAV capsid proteins (53.7% coverage), but none from nonstructural proteins, indicating capsids are packaged as cargo into eHAV vesicles via a highly specific sorting process. Other eHAVassociated proteins (n = 105) were significantly enriched for components of the endolysosomal system (>60%, P < 0.001) and included many common exosome-associated proteins such as the tetraspanin CD9 and dipeptidyl peptidase 4 (DPP4) along with multiple endosomal sorting complex required for transport III (ESCRT-III)-associated proteins. Immunoprecipitation confirmed that DPP4 is displayed on the surface of eHAV produced in cell culture or present in sera from humans with acute hepatitis A. No LC3-related peptides were identified by mass spectrometry. RNAi depletion studies confirmed that ESCRT-III proteins, particularly CHMP2A, function in eHAV biogenesis. In addition to identifying surface markers of eHAV vesicles, the results support an exosome-like mechanism of eHAV egress involving endosomal budding of HAV capsids into multivesicular bodies.exosome | multivesicular body | ESCRT | extracellular vesicle | picornavirus T he Picornaviridae are a large and diverse family of positivestrand RNA viruses that include numerous pathogens (1). Classically considered "nonenveloped," these viruses package their single-stranded genomes within stable icosahedral protein capsids that are released from cells following cell lysis. However, recent work has revealed that several picornaviruses gain egress from cells in a nonlytic fashion within the lumen of extracellular vesicles shed from the cell. Most notably, hepatitis A virus (HAV; genus Hepatovirus), an important cause of enterically transmitted hepatitis in humans, replicates without cytopathic effect and is released from cells as membrane-wrapped, "quasienveloped" (eHAV) virions similar in size and density to exosomes (2). eHAV virions have been identified in sera collected from persons with acute hepatitis A, as well as in supernatant fluids of infected cell cultures. These virions are completely cloaked in host-derived membranes that protect the capsid from neutralizing antibody until the quasi-envelope is degraded wi...

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Protein composition of the hepatitis A virus quasi-envelope

McKnight

Xie

González‐López

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

124

View full text Add to dashboard Cite

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“…The endosomal sorting complexes required for transport (ESCRTs) 2 participate in multivesicular body (MVB) sorting in the endocytic pathway, abscission of the cellular bridge during cytokinesis, the budding of enveloped viruses, and the repair of small wounds in the plasma membrane (1)(2)(3)(4)(5). Most of these processes are similar in that cytosolic machinery (i.e.…”

mentioning

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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“…[1][2][3][4][5][6][7][8][9]. ESCRT factors are recruited to their different sites of action by sequential protein-protein and protein-membrane interactions that are initiated by membrane-specific adaptors such as the HRS-STAM complex (multivesicular body vesicle formation), CEP55 (cytokinesis), and retroviral Gag proteins (virus budding).…”

mentioning

confidence: 99%

Interactions of the Human LIP5 Regulatory Protein with Endosomal Sorting Complexes Required for Transport

Skalicky¹,

Arii²,

Wenzel³

et al. 2012

Journal of Biological Chemistry

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Background: LIP5 helps regulate the membrane fission and recycling activities of the ESCRT pathway. Results: Biochemical and structural studies reveal how LIP5 binds different ESCRT-III proteins. Conclusion: ESCRT-III proteins bind independently to different LIP5 sites, and the LIP5-CHMP5 structure reveals a novel interaction mode. Significance: The results help explain how LIP5 can activate VPS4 ATPases to act on ESCRT-III filaments.

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Multivesicular Body Morphogenesis

Cited by 504 publications

References 184 publications

Protein composition of the hepatitis A virus quasi-envelope

Protein composition of the hepatitis A virus quasi-envelope

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

Interactions of the Human LIP5 Regulatory Protein with Endosomal Sorting Complexes Required for Transport

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