Lgd regulates ESCRT-III complex accumulation at multivesicular endosomes to control intralumenal vesicle formation.
Lgd regulates ESCRT-III complex accumulation at multivesicular endosomes to control intralumenal vesicle formation.
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DOI：
10.1091/mbc.e22-08-0342
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发表时间：
2022-12-01
影响因子：
3.3
通讯作者：
Audhya, Anjon
中科院分区：
文献类型：
--
作者：
Clarke, Aryel L.;Lettman, Molly M.;Audhya, Anjon
由ESCRT-III亚基组成的异聚细丝介导的膜重构是发生在多种细胞器中维持细胞稳态的重要过程。进化上保守的Lgd/CC2D1蛋白家族成员被认为调节ESCRT-III聚合物组装，尽管它们的具体作用，特别是在体内的作用尚不清楚。以秀丽隐杆线虫早期胚胎为模型系统，我们发现Lgd/CC2D1定位于内体膜，其缺失损害了内溶酶体货物的分选和降解。在超微结构水平上，Lgd/CC2D1的缺失导致增大的内体腔室的积累，其中包含的腔内囊泡（ILVs）数量减少。然而，与其他ESCRT成分缺失引起的核内体形态异常不同，在缺乏Lgd/CC2D1的胚胎中，ILV大小仅轻微改变。相反，Lgd/CC2D1的缺失会损害ESCRT-III在内体膜上的正常积聚，可能会减慢ILV形成的动力学。总之，我们的研究结果表明，Lgd/CC2D1在ESCRT-III亚基在内体膜上的募集和/或稳定组装中发挥作用，从而促进有效的ILV生物发生。
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.
影响因子：
4.8
作者：
Wang, Lei;Audhya, Anjon
通讯作者：
Audhya, Anjon