title: Adaptor autoregulation promotes coordinated binding within clathrin coats.
abstract: Membrane traffic is an essential process that allows protein and lipid exchange between the endocytic, lysosomal, and secretory compartments. Clathrin-mediated traffic between the trans-Golgi network and endosomes mediates responses to the environment through the sorting of biosynthetic and endocytic protein cargo. Traffic through this pathway is initiated by the controlled assembly of a clathrin-adaptor protein coat on the cytosolic surface of the originating organelle. In this process, clathrin is recruited by different adaptor proteins that act as a bridge between clathrin and the transmembrane cargo proteins to be transported. Interactions between adaptors and clathrin and between different types of adaptors lead to the formation of a densely packed protein network within the coat. A key unresolved issue is how the highly complex adaptor-clathrin interaction and adaptor-adaptor interaction landscape lead to the correct spatiotemporal assembly of the clathrin coat. Here we report the discovery of a new autoregulatory motif within the clathrin adaptor Gga2 that drives synergistic binding of Gga2 to clathrin and the adaptor Ent5. This autoregulation influences the temporal and/or spatial location of the Gga2-Ent5 interaction. We propose that this synergistic binding provides built-in regulation to ensure the correct assembly of clathrin coats.
authors.affiliation: Department of Biology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hung
authors.affiliation: Department of Biology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599.
authors.forename: Quyen L
authors.initials: QL
authors.lastname: Aoh
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Joglekar
authors.affiliation: Department of Biological Chemistry, The David Geffen School of Medicine at the University of California, Los Angeles, California 90095.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Payne
authors.affiliation: Department of Biology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599. Electronic address: mduncan@bio.unc.edu.
authors.forename: Mara C
authors.initials: MC
authors.lastname: Duncan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D001693:Biological Transport, Active / Q000502:physiology; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; C495588:Ent5 protein, S cerevisiae; C497361:Gga2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins