title: Trio, a Rho Family GEF, Interacts with the Presynaptic Active Zone Proteins Piccolo and Bassoon.
abstract: Synaptic vesicles (SVs) fuse with the plasma membrane at a precise location called the presynaptic active zone (AZ). This fusion is coordinated by proteins embedded within a cytoskeletal matrix assembled at the AZ (CAZ). In the present study, we have identified a novel binding partner for the CAZ proteins Piccolo and Bassoon. This interacting protein, Trio, is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) known to regulate the dynamic assembly of actin and growth factor dependent axon guidance and synaptic growth. Trio was found to interact with the C-terminal PBH 9/10 domains of Piccolo and Bassoon via its own N-terminal Spectrin repeats, a domain that is also critical for its localization to the CAZ. Moreover, our data suggest that regions within the C-terminus of Trio negatively regulate its interactions with Piccolo/Bassoon. These findings provide a mechanism for the presynaptic targeting of Trio and support a model in which Piccolo and Bassoon play a role in regulating neurotransmission through interactions with proteins, including Trio, that modulate the dynamic assembly of F-actin during cycles of synaptic vesicle exo- and endocytosis.
authors.affiliation: Dept. of Psychiatry and Behavioral Science, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California, United States of America.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Terry-Lorenzo
authors.affiliation: Dept. of Psychiatry and Behavioral Science, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California, United States of America.|Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile, Alameda, Santiago, Chile.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Torres
authors.affiliation: Dept. of Psychiatry and Behavioral Science, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California, United States of America.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Wagh
authors.affiliation: Dept. of Psychiatry and Behavioral Science, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California, United States of America.
authors.forename: Jose
authors.initials: J
authors.lastname: Galaz
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Dept. of Psychiatry and Behavioral Science, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California, United States of America.
authors.forename: Clarissa L
authors.initials: CL
authors.lastname: Waites
authors.affiliation: Dept. of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.affiliation: Dept. of Neurology and Neurological Sciences Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Reimer
authors.affiliation: Dept. of Psychiatry and Behavioral Science, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California, United States of America.|German Centers for Neurodegenerative Diseases, Charité - Medical University, Berlin, Germany.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Garner
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D004705:Endocytosis; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000199:Actins; C113688:Bsn protein, rat; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C405514:Pclo protein, rat; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human