Fath K R, Burgess D R
Department of Biological Sciences, University of Pittsburgh, Pennsylvania 15260.
J Cell Biol. 1993 Jan;120(1):117-27. doi: 10.1083/jcb.120.1.117.
In the intestinal brush border, the mechanoenzyme myosin-I links the microvillus core actin filaments with the plasma membrane. Previous immunolocalization shows that myosin-I is associated with vesicles in mature enterocytes (Drenckhahn, D., and R. Dermietzel. 1988. J. Cell Biol. 107:1037-1048) suggesting a potential role mediating vesicle motility. We now report that myosin-I is associated with Golgi-derived vesicles isolated from cells that are rapidly assembling brush borders in intestinal crypts. Crypt cells were isolated in hyperosmotic buffer, homogenized, and fractionated using differential- and equilibrium-density centrifugation. Fractions containing 50-100-nm vesicles, a similar size to those observed in situ, were identified by EM and were shown to contain myosin-I as demonstrated by immunoblotting and immunolabel negative staining. Galactosyltransferase, a marker enzyme for trans-Golgi membranes was present in these fractions, as was alkaline phosphatase, which is an apical membrane targeted enzyme. Galactosyltransferase was also present in vesicles immuno-purified with antibodies to myosin-I. Villin, a marker for potential contamination from fragmented microvilli, was absent. Myosin-I was found to reside on the vesicle "outer" or cytoplasmic surface for it was accessible to exogenous proteases and intact vesicles could be immunolabeled with myosin-I antibodies in solution. The bound myosin-I could be extracted from the vesicles using NaCl, KI and Na2CO3, suggesting that it is a vesicle peripheral membrane protein. These vesicles were shown to bundle actin filaments in an ATP-dependent manner. These results are consistent with a role for myosin-I as an apically targeted motor for vesicle translocation in epithelial cells.
在肠刷状缘,机械酶肌球蛋白-I将微绒毛核心肌动蛋白丝与质膜相连。先前的免疫定位显示,肌球蛋白-I与成熟肠细胞中的囊泡相关(德伦卡恩,D.,和R. 德米策尔。1988年。《细胞生物学杂志》107:1037 - 1048),提示其在介导囊泡运动中可能发挥作用。我们现在报告,肌球蛋白-I与从肠道隐窝中快速组装刷状缘的细胞中分离出的高尔基体衍生囊泡相关。隐窝细胞在高渗缓冲液中分离,匀浆,并使用差速离心和平衡密度离心进行分级分离。通过电子显微镜鉴定出含有50 - 100纳米囊泡的级分,其大小与原位观察到的相似,并通过免疫印迹和免疫标记负染色显示含有肌球蛋白-I。反式高尔基体膜的标记酶半乳糖基转移酶存在于这些级分中,作为顶端膜靶向酶的碱性磷酸酶也存在。半乳糖基转移酶也存在于用肌球蛋白-I抗体免疫纯化的囊泡中。绒毛蛋白,一种来自破碎微绒毛潜在污染的标记物,不存在。发现肌球蛋白-I位于囊泡的“外部”或细胞质表面,因为它可被外源性蛋白酶作用,完整的囊泡可在溶液中用肌球蛋白-I抗体进行免疫标记。结合的肌球蛋白-I可用氯化钠、碘化钾和碳酸钠从囊泡中提取,表明它是一种囊泡外周膜蛋白。这些囊泡显示以ATP依赖的方式使肌动蛋白丝成束。这些结果与肌球蛋白-I作为上皮细胞中囊泡转运的顶端靶向马达的作用一致。