ミタニ シヨウヘイ   MITANI Shohei
  三谷 昌平
   所属   医学部 医学科
   職種   教授・講座主任
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Structure and function analysis of the C. elegans aminophospholipid translocase TAT-1.
掲載誌名 正式名:Journal of cell science
略  称:J Cell Sci
ISSNコード:(1477-9137)0021-9533(Linking)
掲載区分国外
巻・号・頁 132(5),1-7頁
著者・共著者 Chen Yu-Zen, Klöditz Katharina, Lee Eui-Seung, Nguyen Diemmy Pham, Yuan Quan, Johnson Jack, Lee-Yow Yannick, Hall Adam, Mitani Shohei, Xia Ning-Shao, Fadeel Bengt, Xue Ding
発行年月 2019/02
概要 The Caenorhabditis elegans aminophospholipid translocase TAT-1 maintains phosphatidylserine (PS) asymmetry in the plasma membrane and regulates endocytic transport. Despite these important functions, the structure-function relationship of this protein is poorly understood. Taking advantage of the tat-1 mutations identified by the C. elegans million mutation project, we investigated the effects of 16 single amino acid substitutions on the two functions of the TAT-1 protein. Two substitutions that alter a highly conserved PISL motif in the fourth transmembrane domain and a highly conserved DKTGT phosphorylation motif, respectively, disrupt both functions of TAT-1, leading to a vesicular gut defect and ectopic PS exposure on the cell surface, whereas most other substitutions across the TAT-1 protein, often predicted to be deleterious by bioinformatics programs, do not affect the functions of TAT-1. These results provide in vivo evidence for the importance of the PISL and DKTGT motifs in P4-type ATPases and improve our understanding of the structure-function relationship of TAT-1. Our study also provides an example of how the C. elegans million mutation project helps decipher the structure, functions, and mechanisms of action of important genes.
DOI 10.1242/jcs.227660
PMID 30683797