title: Transmembrane protein 139 (TMEM139) interacts with human kidney isoform of anion exchanger 1 (kAE1).
abstract: Human kidney anion exchanger 1 (kAE1) mediates Cl(-)/HCO3(-) exchanges at the basolateral membrane of the acid-secreting α-intercalated cells. Mutations in SLC4A1 gene encoding kAE1 are associated with distal renal tubular acidosis (dRTA). Several studies have shown that impaired trafficking of the mutant kAE1 is an important molecular mechanism underlying the pathogenesis of dRTA. Proteins involved in kAE1 trafficking were identified but the mechanism resulting in dRTA remained unclear. Thus, this study attempted to search for additional proteins interacting with C-terminal of kAE1 (Ct-kAE1) and involved in kAE1 trafficking to cell membrane. Transmembrane protein 139 (TMEM139) was identified as a protein interacting with Ct-kAE1 by yeast two-hybrid screening. The interaction between kAE1 and TMEM139 was confirmed by affinity co-purification, co-immunoprecipitation (co-IP) and yellow fluorescent protein (YFP)-based protein fragment complementation assay (PCA). In addition, flow cytometry results showed that suppression of endogenous TMEM139 by small interfering RNA (siRNA) and over-expression of TMEM139 in HEK293T cells could reduce and increase membrane localization of kAE1, respectively. The presented data demonstrate that TMEM139 interacts with kAE1 and promotes its intracellular trafficking.
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhon Pathom 73170, Thailand.
authors.forename: Nalin-On
authors.initials: NO
authors.lastname: Nuiplot
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Mutita
authors.initials: M
authors.lastname: Junking
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Natapol
authors.initials: N
authors.lastname: Duangtum
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Sasiprapa
authors.initials: S
authors.lastname: Khunchai
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Nunghathai
authors.initials: N
authors.lastname: Sawasdee
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhon Pathom 73170, Thailand. Electronic address: varaporn.akk@mahidol.ac.th.
authors.forename: Varaporn
authors.initials: V
authors.lastname: Akkarapatumwong
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D008565:Membrane Proteins; D020033:Protein Isoforms; C000602393:TMEM139 protein, human
keywords: Kidney isoform of anion exchanger 1 (kAE1); Protein trafficking; Protein–protein interaction; Transmembrane protein 139 (TMEM139); Yeast two-hybrid (Y2H) system