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Regulation of ESCRT endosomal recruitment by the lipid-binding protein ALIX

Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. 5220 - 2018/05/25
Abstract The endosomal sorting complexes required for transport (ESCRT) is a multiprotein complex that participates in processes which require membrane deformation, such as cytokinetic abscission, and multivesicular body (MVB) biogenesis. MVBs contain intraluminal vesicles (ILV), the formation of which plays a key role in the delivery of ubiquitinated cargo to lysosomes for degradation. ALIX is an ESCRT-associated protein known to interact with TSG101 and CHMP4, two ESCRTs, and a late endosomal lipid, LBPA. ALIX and LBPA participate in ILV formation, yet the mechanism by which they act is unknown. Here, we show that ALIX recruits ESCRT proteins, mainly CHMP4, to late endosomes, in an LBPA-dependent manner. Additionally, ALIX overexpression induces the endosomal accumulation of ubiquitinated proteins, providing evidence that the sorting of several specific transmembrane proteins depends on ALIX. Altogether, we illustrate the importance of ALIX and LBPA in the recruitment of ESCRTs and in the sorting of specific cargo.
URN: urn:nbn:ch:unige-1069227
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Thesis (6.3 MB) - public document Free access
Research group Groupe Gruenberg
Swiss National Science Foundation: 31003A_159479
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LARIOS, Jorge. Regulation of ESCRT endosomal recruitment by the lipid-binding protein ALIX. Université de Genève. Thèse, 2018. doi: 10.13097/archive-ouverte/unige:106922 https://archive-ouverte.unige.ch/unige:106922

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Deposited on : 2018-08-08

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