title: Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression.
abstract: Most cells in tissues are polarized and usually have two distinct plasma membrane domains-an apical membrane and a basolateral membrane, which are the result of polarized trafficking of proteins and lipids. However, the mechanism underlying the cell polarization is not fully understood. In this study, we investigated the involvement of synaptotagmin-like protein 2-a (Slp2-a), an effector molecule for the small GTPase Rab27, in polarized trafficking by using Madin-Darby canine kidney II cells as a model of polarized cells. The results show that the level of Slp2-a expression in MDCK II cells increases greatly as the cells become polarized and that its expression is specifically localized at the apical membrane. The results also reveal that Slp2-a is required for targeting of the signaling molecule podocalyxin to the apical membrane in a Rab27A-dependent manner. In addition, ezrin, a downstream target of podocalyxin, and ERK1/2 are activated in Slp2-a-knockdown cells, and their activation results in a dramatic reduction in the amount of the tight junction protein claudin-2. Because both Slp2-a and claudin-2 are highly expressed in mouse renal proximal tubules, Slp2-a is likely to regulate claudin-2 expression through trafficking of podocalyxin to the apical surface in mouse renal tubule epithelial cells.
authors: Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors: Takao
authors: T
authors: Yasuda
authors: Chika
authors: C
authors: Saegusa
authors: Sachiko
authors: S
authors: Kamakura
authors: Hideki
authors: H
authors: Sumimoto
authors: Mitsunori
authors: M
authors: Fukuda
mesh_terms: D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004285:Dogs; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D012795:Sialoglycoproteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins; D000099149:Ezrin
chemical_list: D057167:Claudins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D012795:Sialoglycoproteins; D020691:rab GTP-Binding Proteins; D000075745:rab27 GTP-Binding Proteins; D000099149:Ezrin; C113371:Cldn2 protein, mouse; C424134:Sytl2 protein, mouse; C001643:podocalyxin; C512962:Rab27a protein, mouse