Molecular Mechanisms of the Membrane Sculpting ESCRT Pathway

Abstract

The endosomal sorting complexes required for transport (ESCRT) drive multivesicular body (MVB) biogenesis and cytokinetic abscission. Originally identified through genetics and cell biology, more recent work has begun to elucidate the molecular mechanisms of ESCRTmediated membrane remodeling, with special focus on the ESCRT-III complex. In particular, several light and electron microscopic studies provide high-resolution imaging of ESCRT-III rings and spirals that purportedly drive MVB morphogenesis and abscission. These studies highlight unifying principles to ESCRT-III function, in particular: (1) the ordered assembly of the ESCRT-III monomers into a heteropolymer, (2) ESCRT-III as a dynamic complex, and (3) the role of the AAA ATPase Vps4 as a contributing factor in membrane scission. Mechanistic comparisons of ESCRT-III function in MVB morphogenesis and cytokinesis suggest common mechanisms in membrane remodeling. THE ESCRT PATHWAY IN MVB BIOGENESIS AND CYTOKINESIS

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

“…In our in vivo experiments, we have observed a decrease in Hh signalling by knocking down Vps22, an ESCRT-II complex component described as dispensable for vesicles derived directly from the plasma membrane 33,34 , but required for MVB formation 35 (reviewed in ref. 36) supporting an MVB fusion origin. However, we have also observed a decrease in signalling and Hh release when interfering with P4-ATPase (CG31729), the Drosophila orthologue of TAT-5 specifically involved in the formation of ectosomes in C. elegans 24 .…”

ESCRT-I Component VPS23A Affects ABA Signaling by Recognizing ABA Receptors for Endosomal Degradation

“…4 endosomal sorting complex and is required for the transport (ESCRTs) machinery that includes ESCRT-0, ESCRT-I, ESCRT-II and ESCRT-III complexes and is subsequently sequestered into vacuoles/lysosomes for degradation by luminal proteases (Henne et al, 2013;Shields and Piper, 2011). Although homologs of most ESCRT 0-III complex components occurring in yeast and mammals are found in the Arabidopsis genome (Barberon et al, 2014;Hurley and Emr, 2006), the functions of only a few of these homologs have been explored.…”

Lipid Sorting and Multivesicular Endosome Biogenesis

“…1) (Gruenberg 2001;Huotari and Helenius 2011). This process is interesting from a mechanistic and topological point of view, because it occurs in a direction opposite to classical membrane budding leading to vesicle or tubule formation in both the secretory and endocytic pathways Henne et al 2013). Eventually, these multivesicular regions mature or detach from early endosomes and become free multivesicular endosomes, often referred to as multivesicular bodies or endosomal carrier vesicles (MVBs/ECVs), which deliver their ILV cargo to late endosomes and lysosomes for degradation.…”