VPS37 Isoforms Differentially Modulate the Ternary Complex Formation of ALIX, ALG-2, and ESCRT-I

Okumura, Mayumi; Katsuyama, Angela M.; Shibata, Hideki; Maki, Masatoshi

doi:10.1271/bbb.130280

Cited by 26 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the well characterized involvement of ESCRT proteins and ubiquitination pathway in viral budding [29, 30], we propose that in the flagella ubiquitinated proteins are clustered by a mechanism involving Alix and PDCD6 [31, 32], which can form a ternary complex with ESCRT-I [33]. These ubiquitinated proteins are then concentrated in membrane buds that are released into the medium by a mechanism involving ESCRT-III proteins and VPS4 [28, 34].…”

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Ciliary Membranes and Ectosomes

et al. 2016

View full text Add to dashboard Cite

Summary Primary and motile cilia/flagella function as cellular antennae, receiving signals from the environment, and subsequently activating signaling pathways that are critical for cellular homeostasis and differentiation [1-3]. Recent work with the green alga Chlamydomonas and the nematode C. elegans demonstrated that ectosomes can be released from the cilium and can mediate the intercellular communication [4-9]. To better understand the function of flagellar ectosomes, we have compared their protein composition to that of the flagellar membrane from which they are derived. Ectosomes released from flagella have a unique protein composition, being enriched in a subset of flagellar membrane proteins, proteases, proteins from the endosomal sorting complex required for transport (ESCRT) [10-12], small GTPases, and ubiquitinated proteins. Live imaging showed that an ESCRT-related protein (PDCD6) was enriched in ectosomes released from flagella during gamete activation. We devised a sensitive and rapid assay to monitor ectosome release using luciferase fused to PDCD6 and a mutated ubiquitin. Ectosome release increased when cells underwent flagellar resorption. Knockdown of two ESCRT-related proteins, PDCD6 and VPS4, attenuated ectosome release during flagellar shortening and shortening was slowed. These data suggest that the ESCRT proteins mediate ectosome release and thereby influence flagellar shortening in Chlamydomonas. In addition, the prevalence of receptors such as agglutinin and ubiquitinated proteins in ciliary ectosomes suggests that they are involved in cell signaling and turnover of ciliary proteins.

show abstract

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Ciliary Membranes and Ectosomes

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This, and other overlapping functions of CD63, syntenin-1 and ALIX such as viral egress from cells, ubiquitin-independent sorting of transmembrane cargos to MVEs5262, suggest diverse cellular functionality of the complex. Previous studies demonstrated that ALIX interacts with TSG1016364, an ESCRT-I protein binding to the HPV minor capsid component L232. Therefore, spatial juxtaposition of ALIX with endocytosed viruses may be important for the subsequent egress of disassembled virions from MVEs to the Golgi.…”

Section: Discussionmentioning

confidence: 99%

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses

Gräßel

Fast

Scheffer

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

show abstract

“…ALIX Bro1 also can bind membranes, particularly lysobisphosphatidic acid (LBPA) (Bissig et al, 2013), and may help stabilize (or drive) membrane curvature at bud necks owing to its crescent shape (Kim et al, 2005; Pires et al, 2009). The activities of different Bro1 family members can be modulated by a series of auxiliary domains and inputs, including: 1) calcium and calcium-responsive binding partners (ALIX) (Bissig et al, 2013; Okumura et al, 2013); 2) downstream V domains (in ALIX/Bro1p and HD-PTP) that can bind both ubiquitin (Dowlatshahi et al, 2012; Keren-Kaplan et al, 2013; Pashkova et al, 2013) and YPXL motifs (see below); 3) autoinhibitory elements and their activating partners (ALIX) (Zhai et al, 2011a; Zhou et al, 2010); and 4) post-translational modifications such as ubiquitylation (ALIX) and farnesylation (BROX).…”

Section: The Escrt Pathwaymentioning

confidence: 99%

Virus Budding and the ESCRT Pathway

Votteler

Sundquist

2013

Cell Host & Microbe

477

514

View full text Add to dashboard Cite

Enveloped viruses escape infected cells by budding through limiting membranes. In the decade since the discovery that the Human Immunodeficiency Virus (HIV) recruits cellular ESCRT (endosomal sorting complexes required for transport) machinery to facilitate viral budding, this pathway has emerged as the major escape route for enveloped viruses. In cells, the ESCRT pathway catalyzes the analogous membrane fission events required for the abscission stage of cytokinesis and for a series of “reverse topology” vesiculation events. Studies of enveloped virus budding are therefore providing insights into the complex cellular mechanisms of cell division and membrane protein trafficking (and vice versa). Here, we review how viruses mimic cellular recruiting signals to usurp the ESCRT pathway, discuss mechanistic models for ESCRT pathway functions, and highlight important research frontiers.

show abstract

VPS37 Isoforms Differentially Modulate the Ternary Complex Formation of ALIX, ALG-2, and ESCRT-I

Cited by 26 publications

References 33 publications

Comparative Analysis of Ciliary Membranes and Ectosomes

Comparative Analysis of Ciliary Membranes and Ectosomes

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses

Virus Budding and the ESCRT Pathway

Contact Info

Product

Resources

About