title: PICK1 is implicated in organelle motility in an Arp2/3 complex-independent manner.
abstract: PICK1 is a modular scaffold implicated in synaptic receptor trafficking. It features a PDZ domain, a BAR domain, and an acidic C-terminal tail (ACT). Analysis by small- angle x-ray scattering suggests a structural model that places the receptor-binding site of the PDZ domain and membrane-binding surfaces of the BAR and PDZ domains adjacent to each other on the concave side of the banana-shaped PICK1 dimer. In the model, the ACT of one subunit of the dimer interacts with the PDZ and BAR domains of the other subunit, possibly accounting for autoinhibition. Consistently, full-length PICK1 shows diffuse cytoplasmic localization, but it clusters on vesicle-like structures that colocalize with the trans-Golgi network marker TGN38 upon deletion of either the ACT or PDZ domain. This localization is driven by the BAR domain. Live-cell imaging further reveals that PICK1-associated vesicles undergo fast, nondirectional motility in an F-actin-dependent manner, but deleting the ACT dramatically reduces vesicle speed. Thus the ACT links PICK1-associated vesicles to a motility factor, likely myosin, but, contrary to previous reports, PICK1 neither binds nor inhibits Arp2/3 complex.
authors: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Yadaiah
authors: Y
authors: Madasu
authors: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
authors: Changsong
authors: C
authors: Yang
authors: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Malgorzata
authors: M
authors: Boczkowska
authors: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Kelley A
authors: KA
authors: Bethoney
authors: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Adam
authors: A
authors: Zwolak
authors: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Grzegorz
authors: G
authors: Rebowski
authors: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
authors: Tatyana
authors: T
authors: Svitkina
authors: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 droberto@mail.med.upenn.edu.
authors: Roberto
authors: R
authors: Dominguez
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D022161:Transport Vesicles / Q000378:metabolism / Q000502:physiology*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D002352:Carrier Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human
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