Lgd regulates ESCRT-III complex accumulation at multivesicular endosomes to control intralumenal vesicle formation

Membrane remodeling mediated by heteropolymeric filaments composed of ESCRT-III subunits is an essential process that occurs at a variety of organelles to maintain cellular homeostasis. Members of the evolutionarily conserved Lgd/CC2D1 protein family have been suggested to regulate ESCRT-III polymer assembly, although their specific roles, particularly in vivo, remain unclear. Using the Caenorhabditis elegans early embryo as a model system, we show that Lgd/CC2D1 localizes to endosomal membranes, and its loss impairs endolysosomal cargo sorting and degradation. At the ultrastructural level, the absence of Lgd/CC2D1 results in the accumulation of enlarged endosomal compartments that contain a reduced number of intralumenal vesicles (ILVs). However, unlike aberrant endosome morphology caused by depletion of other ESCRT components, ILV size is only modestly altered in embryos lacking Lgd/CC2D1. Instead, loss of Lgd/CC2D1 impairs normal accumulation of ESCRT-III on endosomal membranes, likely slowing the kinetics of ILV formation. Together, our findings suggest a role for Lgd/CC2D1 in the recruitment and/or stable assembly of ESCRT-III subunits on endosomal membranes to facilitate efficient ILV biogenesis.

Movie S1: Lgd dynamics during early embryogenesis. Timelapse confocal imaging taken in utero of a GFP fusion to Lgd during early zygotic development. Playback rate, 48x.

https://ascb-prod-streaming.literatumonline.com/journals/content/mboc/0/mboc.ahead-of-print/mbc.e22-08-0342/20221024/media/mc-e22-08-0342-s01.,1200,960,900,768,652,642,.mp4.m3u8?b92b4ad1b4f274c7087751841cabb28b19a3e23570e4794628d00a388fabd4f47061f4b4b81c11dac4c336cd5be6a2a6a495e5def8479aeedf32e6f4ec8f325c8354b92f9a15e63bba6a844857b79852090ccd89a2b2f5b23fa9eac19a4eee9b3b8b8590b041aaa99dde075e0f8f8a92f382ac8f493da301d8ad333f948f593dc35ea8572d252d4d43c84d867a568a6b478908924a7603ad36213c40ff8ae3d8ae4afbfa8705ab6335434b78bafef30d1d99

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