Decreased expression of cortactin in the schizophrenia brain.

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 62kDa isoform was decreased by 43%; the 71kDa isoform was decreased by 32%; and the 58kDa 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.