Premium
Role of Adaptor Proteins and Clathrin in the Trafficking of Human Kidney Anion Exchanger 1 ( kAE1 ) to the Cell Surface
Author(s) -
Junking Mutita,
Sawasdee Nunghathai,
Duangtum Natapol,
Cheunsuchon Boonyarit,
Limjindaporn Thawornchai,
Yenchitsomanus Pathai
Publication year - 2014
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12172
Subject(s) - biology , clathrin , signal transducing adaptor protein , microbiology and biotechnology , intercalated cell , transport protein , epithelial polarity , apical membrane , immunogold labelling , endocytosis , signal transduction , biochemistry , secretion , cell , immunology , membrane , antibody
Kidney anion exchanger 1 ( kAE1 ) plays an important role in acid–base homeostasis by mediating chloride/bicarbornate (Cl − / HCO 3 − ) exchange at the basolateral membrane of α‐intercalated cells in the distal nephron. Impaired intracellular trafficking of kAE1 caused by mutations of S LC4A1 encoding kAE1 results in kidney disease – distal renal tubular acidosis ( dRTA ). However, it is not known how the intracellular sorting and trafficking of kAE1 from trans‐Golgi network ( TGN ) to the basolateral membrane occurs. Here, we studied the role of basolateral‐related sorting proteins, including the mu1 subunit of adaptor protein ( AP ) complexes, clathrin and protein kinase D, on kAE1 trafficking in polarized and non‐polarized kidney cells. By using RNA interference, co‐immunoprecipitation, yellow fluorescent protein‐based protein fragment complementation assays and immunofluorescence staining, we demonstrated that AP ‐1 mu1A , AP ‐3 mu1, AP ‐4 mu1 and clathrin (but not AP ‐1 mu1B , PKD1 or PKD2 ) play crucial roles in intracellular sorting and trafficking of kAE1 . We also demonstrated colocalization of kAE1 and basolateral‐related sorting proteins in human kidney tissues by double immunofluorescence staining. These findings indicate that AP ‐1 mu1A , AP ‐3 mu1, AP ‐4 mu1 and clathrin are required for kAE1 sorting and trafficking from TGN to the basolateral membrane of acid‐secreting α‐intercalated cells.