PALS1 specifies the localization of ezrin to the apical membrane of gastric parietal cells.
The ERM (ezrin/radixin/moesin) proteins provide a regulated linkage between membrane proteins and the cortical cytoskeleton and also participate in signal transduction pathways. Ezrin is localized to the apical membrane of parietal cells and couples the protein kinase A activation cascade to regulated HCl secretion in gastric parietal cells. Here, we show that the integrity of ezrin is essential for parietal cell activation and provide the first evidence that ezrin interacts with PALS1, an evolutionarily conserved PDZ and SH3 domain-containing protein. Our biochemical study verifies that ezrin binds to PALS1 via its N terminus and is co-localized with PALS1 to the apical membrane of gastric parietal cells. Furthermore, our study shows that PALS1 is essential for the apical localization of ezrin, as either suppression of PALS1 protein accumulation or deletion of the PALS1-binding domain of ezrin eliminated the apical localization of ezrin. Finally, our study demonstrates the essential role of ezrin-PALS1 interaction in the apical membrane remodeling associated with parietal cell secretion. Taken together, these results define a novel molecular mechanism linking ezrin to the conserved apical polarity complexes and their roles in polarized epithelial secretion of gastric parietal cells.
Cao
Xinwang
X
School of Life Science, University of Science and Technology of China, Hefei 230027, Peoples Republic of China.
Ding
Xia
X
Guo
Zhen
Z
Zhou
Rihong
R
Wang
Fengsong
F
Long
Fei
F
Wu
Fang
F
Bi
Feng
F
Wang
Qichen
Q
Fan
Daiming
D
Forte
John G
JG
Teng
Maikun
M
Yao
Xuebiao
X
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000166:cytology* / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009703:Nucleoside-Phosphate Kinase; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D000099149:Ezrin; C501307:MPP5 protein, human