Structure and function analysis of the C. elegans aminophospholipid translocase TAT-1

J Cell Sci. 2019 Feb 28;132(5):jcs227660. doi: 10.1242/jcs.227660.


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.

Keywords: C. elegans; Endocytic transport; Million mutation project; P4-ATPase; Phosphatidylserine; TAT-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Computational Biology
  • Endocytosis
  • Intestines / physiology*
  • Mutation / genetics
  • Phenotype
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / metabolism*
  • Protein Conformation
  • Protein Transport
  • Structure-Activity Relationship


  • Caenorhabditis elegans Proteins
  • Phospholipid Transfer Proteins
  • TAT-1 protein, C elegans