title: Inactivation of Caenorhabditis elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants.
abstract: In Caenorhabditis elegans, the P4-ATPase TAT-1 and its chaperone, the Cdc50 family protein CHAT-1, maintain membrane phosphatidylserine (PS) asymmetry, which is required for membrane tubulation during endocytic sorting and recycling. Loss of tat-1 and chat-1 disrupts endocytic sorting, leading to defects in both cargo recycling and degradation. In this study, we identified the C. elegans aspartyl aminopeptidase DNPP-1, loss of which suppresses the sorting and recycling defects in tat-1 mutants without reversing the PS asymmetry defect. We found that tubular membrane structures containing recycling cargoes were restored in dnpp-1 tat-1 double mutants and that these tubules overlap with RME-1-positive recycling endosomes. The restoration of the tubular structures in dnpp-1 tat-1 mutants requires normal functions of RAB-5, RAB-10, and RME-1. In tat-1 mutants, we observed alterations in membrane surface charge and targeting of positively charged proteins that were reversed by loss of dnpp-1. DNPP-1 displays a specific aspartyl aminopeptidase activity in vitro, and its enzymatic activity is required for its function in vivo. Our data reveal the involvement of an aminopeptidase in regulating endocytic sorting and recycling and suggest possible roles of peptide signaling and/or protein metabolism in these processes.
authors: College of Biological Sciences, China Agricultural University, Beijing 100094, China.
authors: Xin
authors: X
authors: Li
authors: Baohui
authors: B
authors: Chen
authors: Sawako
authors: S
authors: Yoshina
authors: Tanxi
authors: T
authors: Cai
authors: Fuquan
authors: F
authors: Yang
authors: Shohei
authors: S
authors: Mitani
authors: Xiaochen
authors: X
authors: Wang
mesh_terms: D000626:Aminopeptidases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology; D007422:Intestines / Q000166:cytology; D007700:Kinetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009928:Organ Specificity; D010718:Phosphatidylserines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D029742:Caenorhabditis elegans Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D000626:Aminopeptidases; C583998:DNPP-1 protein, C elegans; C522446:TAT-1 protein, C elegans