Regulation of endocytic clathrin dynamics by cargo ubiquitination.
Regulation of endocytic clathrin dynamics by cargo ubiquitination.
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DOI：
10.1016/j.devcel.2012.08.003
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发表时间：
2012-09-11
影响因子：
11.8
通讯作者：
von Zastrow, Mark
中科院分区：
文献类型：
--
作者：
Henry, Anastasia G.;Hislop, James N.;Grove, Joe;Thorn, Kurt;Marsh, Mark;von Zastrow, Mark
一些内吞货物控制网格蛋白包被的小窝（CCP）的成熟，但它是不知道如何调节沟通。我们发现μ-阿片神经肽受体通过泛素化向其封闭的CCP传递信号。非泛素化受体延迟CCP在成熟的中间阶段，网格蛋白晶格组装完成后，但在膜断裂。受体泛素化解除这种抑制，有效地触发CCP断裂，并产生含有受体的内吞囊泡。传递这种内吞促进信号的泛素修饰被添加到受体的第一个细胞质环，由Smurf 2泛素连接酶催化，并通过内吞衔接子β-抑制蛋白的Smurf 2募集与活化依赖性受体磷酸化和聚集协调。Epsin 1检测CCP处的信号，并且是泛素促进的断裂所需的。这种货物到外套通信系统介导的生化检查点，确保适当的受体泛素化，为以后的贩运，它控制特定的受体加载到CCP时，达到足够的法定人数的传感。E3连接酶Smurf 2引起的β μ-阿片受体（莫尔）泛素化触发内吞作用非泛素化MOR延长网格蛋白包被的小凹（CCP）的表面寿命CCP的动力学控制确保受体泛素化用于胞内后运输CCP的动力学控制也有助于确定内吞货物负荷一些内吞货物调节网格蛋白包被的小凹（CCP）成熟，但这种调节如何被传达仍然未知。亨利等人显示μ-阿片受体通过泛素化向其封闭的CCP发信号，允许货物介导的CCP动力学控制。作者认为，这调节了CCP的受体负荷，随后调节了受体运输。
Some endocytic cargoes control clathrin-coated pit (CCP) maturation, but it is not known how such regulation is communicated. We found that μ-opioid neuropeptide receptors signal to their enclosing CCPs by ubiquitination. Nonubiquitinated receptors delay CCPs at an intermediate stage of maturation, after clathrin lattice assembly is complete but before membrane scission. Receptor ubiquitination relieves this inhibition, effectively triggering CCP scission and producing a receptor-containing endocytic vesicle. The ubiquitin modification that conveys this endocytosis-promoting signal is added to the receptor’s first cytoplasmic loop, catalyzed by the Smurf2 ubiquitin ligase, and coordinated with activation-dependent receptor phosphorylation and clustering through Smurf2 recruitment by the endocytic adaptor beta-arrestin. Epsin1 detects the signal at the CCP and is required for ubiquitin-promoted scission. This cargo-to-coat communication system mediates a biochemical checkpoint that ensures appropriate receptor ubiquitination for later trafficking, and it controls specific receptor loading into CCPs by sensing when a sufficient quorum is reached. ► μ-opioid receptor (MOR) ubiquitination by the E3 ligase Smurf2 triggers endocytosis ► Nonubiquitinated MORs prolong the surface lifetime of clathrin-coated pits (CCPs) ► Kinetic control of CCPs assures receptor ubiquitination for postendocytic traffic ► Kinetic control of CCPs also helps determine endocytic cargo load Some endocytic cargoes regulate clathrin-coated pit (CCP) maturation, but how such regulation is communicated remains unknown. Henry et al. show that μ-opioid receptors signal to their enclosing CCPs by ubiquitination, allowing cargo-mediated control of CCP dynamics. The authors suggest that this modulates the receptor load of CCPs and, later, receptor trafficking.
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