Eisenberg Evan, Greene Lois E
Laboratory of Cell Biology, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892-0301, USA.
Traffic. 2007 Jun;8(6):640-6. doi: 10.1111/j.1600-0854.2007.00568.x. Epub 2007 May 4.
The ATP-dependent dissociation of clathrin from clathrin-coated vesicles (CCVs) by the molecular chaperone Hsc70 requires J-domain cofactor proteins, either auxilin or cyclin-G-associated kinase (GAK). Both the nerve-specific auxilin and the ubiquitous GAK induce CCVs to bind to Hsc70. The removal of auxilin or GAK from various organisms and cells has provided definitive evidence that Hsc70 uncoats CCVs in vivo. In addition, evidence from various studies has suggested that Hsc70 and auxilin are involved in several other key processes that occur during clathrin-mediated endocytosis. First, Hsc70 and auxilin are required for the clathrin exchange that occurs during coated-pit invagination and constriction; this clathrin exchange may catalyze any rearrangement of the clathrin-coated pit (CCP) structure that is required during invagination and constriction. Second, Hsc70 and auxilin may chaperone clathrin after it dissociates from CCPs so that it does not aggregate in the cytosol. Third, auxilin and Hsc70 may be involved in the rebinding of clathrin to the plasma membrane to form new CCPs and independently appear to chaperone adaptor proteins so that they can also rebind to membranes to nucleate the formation of new CCPs. Finally, if formation of the curved clathrin coat induces membrane curvature, then Hsc70 and auxilin provide the energy for this curvature by inducing ATP-dependent clathrin exchange and rearrangement during endocytosis and ATP-dependent dissociation of clathrin at the end of the cycle so that it is energetically primed to rebind to the plasma membrane.
分子伴侣Hsc70通过ATP依赖的方式使网格蛋白从网格蛋白包被小泡（CCV）上解离，这一过程需要J结构域辅助因子蛋白，即发动蛋白或细胞周期蛋白G相关激酶（GAK）。神经特异性发动蛋白和普遍存在的GAK都能诱导CCV与Hsc70结合。从各种生物体和细胞中去除发动蛋白或GAK，提供了确凿的证据，证明Hsc70在体内使CCV脱包被。此外，来自各种研究的证据表明，Hsc70和发动蛋白参与了网格蛋白介导的内吞作用过程中发生的其他几个关键过程。首先，在包被凹陷和缢缩过程中发生的网格蛋白交换需要Hsc70和发动蛋白；这种网格蛋白交换可能催化凹陷和缢缩过程中所需的网格蛋白包被凹陷（CCP）结构的任何重排。其次，Hsc70和发动蛋白可能在网格蛋白从CCP解离后对其进行伴侣作用，使其不在细胞质中聚集。第三，发动蛋白和Hsc70可能参与网格蛋白与质膜的重新结合以形成新的CCP，并且独立地似乎对衔接蛋白进行伴侣作用，以便它们也能重新结合到膜上以启动新CCP的形成。最后，如果弯曲的网格蛋白包被的形成诱导膜弯曲，那么Hsc70和发动蛋白通过在内吞作用期间诱导ATP依赖的网格蛋白交换和重排以及在循环结束时诱导ATP依赖的网格蛋白解离，为这种弯曲提供能量，从而使其在能量上准备好重新结合到质膜上。
