Devarajan P, Stabach P R, De Matteis M A, Morrow J S
Department of Pediatrics, Yale University, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10711-6. doi: 10.1073/pnas.94.20.10711.
Spectrin (betaISigma*) and ankyrin (AnkG119) associate with Golgi membranes and the dynactin complex, but their role in vesicle trafficking remains uncertain. We find that the actin-binding domain and membrane-association domain 1 (MAD1) of betaI spectrin together form a constitutive Golgi targeting signal in transfected MDCK cells. Expression of this signal in transfected cells disrupts the endogenous Golgi spectrin skeleton and blocks transport of alpha- and beta-Na,K-ATPase and vesicular stomatitis virus-G protein from the endoplasmic reticulum (ER) but does not disrupt the formation of Golgi stacks, the distribution of beta-COP, or the transport and surface display of E-cadherin. The Golgi spectrin skeleton is thus required for the transport of a subset of membrane proteins from the ER to the Golgi. We postulate that together with polyfunctional adapter proteins such as AnkG119, Golgi spectrin forms a docking complex that acts prior to the cis-Golgi, presumably with vesicular-tubular clusters (VTCs or ERGIC), to sequester specific membrane proteins into vesicles transiting between the ER and Golgi, and subsequently (probably involving other isoforms of spectrin and ankyrin) to mediate cargo transport within the Golgi and to other membrane compartments. We hypothesize that this vesicular spectrin-ankyrin adapter-protein trafficking (or tethering) system (SAATS) mediates the capture and transport of many membrane proteins and acts in conjunction with vesicle-targeting molecules to effect the efficient transport of cargo proteins.
血影蛋白（βISigma*）和锚蛋白（AnkG119）与高尔基体膜和动力蛋白复合体相关联，但其在囊泡运输中的作用仍不确定。我们发现，βI血影蛋白的肌动蛋白结合结构域和膜结合结构域1（MAD1）共同在转染的MDCK细胞中形成一个组成型高尔基体靶向信号。该信号在转染细胞中的表达会破坏内源性高尔基体血影蛋白骨架，并阻断α-和β-Na，K-ATP酶以及水泡性口炎病毒-G蛋白从内质网（ER）的运输，但不会破坏高尔基体堆叠的形成、β-COP的分布或E-钙黏蛋白的运输和表面展示。因此，高尔基体血影蛋白骨架是膜蛋白从内质网运输到高尔基体的一个子集所必需的。我们推测，高尔基体血影蛋白与多官能衔接蛋白如AnkG119一起形成一个对接复合体，该复合体在顺式高尔基体之前起作用，大概是与囊泡管状簇（VTCs或ERGIC）相互作用，将特定的膜蛋白隔离到在内质网和高尔基体之间转运的囊泡中，随后（可能涉及血影蛋白和锚蛋白的其他异构体）介导货物在高尔基体内部以及向其他膜区室的运输。我们假设这种囊泡血影蛋白-锚蛋白衔接蛋白运输（或拴系）系统（SAATS）介导许多膜蛋白的捕获和运输，并与囊泡靶向分子协同作用以实现货物蛋白的高效运输。
