ACAP1 promotes endocytic recycling by recognizing recycling sorting signals.
Cargo sorting that promotes the transport of cargo proteins from a membrane compartment has been predicted to be unlikely in the endocytic recycling pathways. We now show that ACAP1 binds specifically and directly to recycling cargo proteins. Reducing this interaction for TfR inhibits its recycling. Moreover, ACAP1 binds to two distinct phenylalanine-based sequences in the cytoplasmic domain of TfR that function as recycling sorting signals to promote its transport from the recycling endosome. Taken together, these findings indicate that ACAP1 promotes cargo sorting by recognizing recycling sorting signals.
Dai
Jun
J
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Li
Jian
J
Bos
Erik
E
Porcionatto
Marimelia
M
Premont
Richard T
RT
Bourgoin
Sylvain
S
Peters
Peter J
PJ
Hsu
Victor W
VW
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D005456:Fluorescent Dyes; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009930:Organic Chemicals; D017354:Point Mutation; D011233:Precipitin Tests; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D011990:Receptors, Transferrin / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; C417664:Alexa594; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D020690:GTPase-Activating Proteins; D009930:Organic Chemicals; D021382:Protein Sorting Signals; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase; D020727:ADP-Ribosylation Factors; D000409:Alanine