title: Decreased expression of cortactin in the schizophrenia brain.
abstract: Schizophrenia is a severe psychiatric disorder that is characterized by a wide array of symptoms and a complex neuropathology. A well-characterized neurobiological feature of schizophrenia is abnormal synaptic plasticity, although the mechanisms underlying this are not fully understood. Numerous studies have demonstrated a link between proper functioning of the cytoskeleton and synaptic plasticity. The actin-related protein-2/3 (Arp2/3) complex is responsible for the nucleation of new actin filaments and elongation of existing actin filaments and is thus crucial to cytoskeletal dynamics, especially actin polymerization and organization. To determine whether the Arp2/3 complex is abnormally expressed in schizophrenia, we measured the protein expression of Arp2 and Arp3, as well as Arp2/3 complex binding partners and associated proteins including cortactin, neuronal-Wiskott-Aldrich syndrome protein (WASP), WASP-family verprolin homologous protein 1 (WAVE1), and Abelson interactor 1 (Abi1) in the superior temporal gyrus of paired schizophrenia and comparison participants. No changes were found in Arp2, Arp3, neuronal-WASP, WAVE1, or Abi1. However, all three isoforms of cortactin were decreased in schizophrenia. Specifically, the 62 kDa isoform was decreased by 43%; the 71 kDa isoform was decreased by 32%; and the 58 kDa isoform was decreased by 35%. Cortactin regulates branching of filamentous actin through its binding and activation of the Arp2/3 complex, and it is thus critical to the formation of stable actin networks. These findings contribute to a growing body of evidence implicating altered cytoskeletal dynamics in schizophrenia.
authors.affiliation: aDepartment of Psychiatry and Behavioral Neurobiology bUniversity Honors Program, University of Alabama at Birmingham, Birmingham, Alabama cDepartment of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Hriday P
authors.initials: HP
authors.lastname: Bhambhvani
authors.forename: Micah
authors.initials: M
authors.lastname: Simmons
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.forename: James H
authors.initials: JH
authors.lastname: Meador-Woodruff
mesh_terms: D051377:Actin-Related Protein 2 / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D051378:Actin-Related Protein 3 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D051356:Cortactin / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*; D014015:Tissue Banks; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
chemical_list: C513733:ABI1 protein, human; C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051376:Actin-Related Protein 2-3 Complex; D051378:Actin-Related Protein 3; D048868:Adaptor Proteins, Signal Transducing; C495868:CTTN protein, human; D051356:Cortactin; D003598:Cytoskeletal Proteins; C495767:WAS protein, human; C114864:WASF1 protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family