title: Endocytic sorting and recycling require membrane phosphatidylserine asymmetry maintained by TAT-1/CHAT-1.
abstract: Endocytic sorting is achieved through the formation of morphologically and functionally distinct sub-domains within early endosomes. Cargoes destined for recycling are sorted to and transported through newly-formed tubular membranes, but the processes that regulate membrane tubulation are poorly understood. Here, we identified a novel Caenorhabditis elegans Cdc50 family protein, CHAT-1, which acts as the chaperone of the TAT-1 P4-ATPase to regulate membrane phosphatidylserine (PS) asymmetry and endocytic transport. In chat-1 and tat-1 mutants, the endocytic sorting process is disrupted, leading to defects in both cargo recycling and degradation. TAT-1 and CHAT-1 colocalize to the tubular domain of the early endosome, the tubular endocytic recycling compartment (ERC), and the recycling endosome where PS is enriched on the cytosolic surface. Loss of tat-1 and chat-1 function disrupts membrane PS asymmetry and abrogates the tubular membrane structure. Our data suggest that CHAT-1 and TAT-1 maintain membrane phosphatidylserine asymmetry, thus promoting membrane tubulation and regulating endocytic sorting and recycling.
authors.affiliation: Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Sheng
authors.initials: S
authors.lastname: Zeng
authors.forename: Jiacong
authors.initials: J
authors.lastname: Yan
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; C522446:TAT-1 protein, C elegans