Knowles Byron C, Weis Victoria G, Yu Shiyan, Roland Joseph T, Williams Janice A, Alvarado Gabriela S, Lapierre Lynne A, Shub Mitchell D, Gao Nan, Goldenring James R
Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37235, USA Department of Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN 37235, USA.
Department of Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN 37235, USA Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37235, USA.
J Cell Sci. 2015 Apr 15;128(8):1617-26. doi: 10.1242/jcs.163303. Epub 2015 Feb 11.
Rab11a is a key component of the apical recycling endosome that aids in the trafficking of proteins to the luminal surface in polarized epithelial cells. Utilizing conditional Rab11a-knockout specific to intestinal epithelial cells, and human colonic epithelial CaCo2-BBE cells with stable Rab11a knockdown, we examined the molecular and pathological impact of Rab11a deficiency on the establishment of apical cell polarity and microvillus morphogenesis. We demonstrate that loss of Rab11a induced alterations in enterocyte polarity, shortened microvillar length and affected the formation of microvilli along the lateral membranes. Rab11a deficiency in enterocytes altered the apical localization of syntaxin 3. These data affirm the role of Rab11a in apical membrane trafficking and the maintenance of apical microvilli in enterocytes.
Rab11a是顶端循环内体的关键组成部分,有助于将蛋白质运输到极化上皮细胞的管腔表面。利用肠道上皮细胞特异性条件性Rab11a敲除技术,以及稳定敲低Rab11a的人结肠上皮CaCo2-BBE细胞,我们研究了Rab11a缺乏对顶端细胞极性建立和微绒毛形态发生的分子和病理影响。我们证明,Rab11a的缺失会诱导肠上皮细胞极性改变、微绒毛长度缩短,并影响沿侧膜的微绒毛形成。肠上皮细胞中Rab11a的缺乏改变了Syntaxin 3的顶端定位。这些数据证实了Rab11a在肠上皮细胞顶端膜运输和顶端微绒毛维持中的作用。