Woodman Philip
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
Biochem J. 2016 Jan 15;473(2):e5-8. doi: 10.1042/BJ20151115.
The multivesicular body (MVB) pathway sorts ubiquitinated membrane cargo to intraluminal vesicles (ILVs) within the endosome, en route to the lysosomal lumen. The pathway involves the sequential action of conserved protein complexes [endosomal sorting complexes required for transport (ESCRTs)], culminating in the activation by ESCRT-II of ESCRT-III, a membrane-sculpting complex. Although this linear pathway of ESCRT activation is widely accepted, a study by Luzio and colleagues in a recent issue of the Biochemical Journal suggests that there is greater complexity in ESCRT-III activation, at least for some MVB cargoes. They show that ubiquitin-dependent sorting of major histocompatibility complex (MHC) class I to the MVB requires the central ESCRT-III complex but does not involve either ESCRT-II or functional links between ESCRT-II and ESCRT-III. Instead, they propose that MHC class I utilizes histidine-domain protein tyrosine phosphatase (HD-PTP), a non-canonical ESCRT interactor, to promote ESCRT-III activation.
多囊泡体（MVB）途径将泛素化的膜货物分选到内体中的腔内小泡（ILV），并将其运输至溶酶体腔。该途径涉及保守蛋白复合物[转运所需的内体分选复合物（ESCRT）]的顺序作用，最终由ESCRT-II激活膜塑形复合物ESCRT-III。尽管ESCRT激活的这种线性途径已被广泛接受，但Luzio及其同事在最近一期《生物化学杂志》上发表的一项研究表明，ESCRT-III激活过程更为复杂，至少对于某些MVB货物来说是这样。他们发现，主要组织相容性复合体（MHC）I类分子向MVB的泛素依赖性分选需要中央ESCRT-III复合物，但不涉及ESCRT-II或ESCRT-II与ESCRT-III之间的功能联系。相反，他们提出MHC I类分子利用组氨酸结构域蛋白酪氨酸磷酸酶（HD-PTP）（一种非典型的ESCRT相互作用分子）来促进ESCRT-III的激活。
