A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: Possible relationship to schizophrenia

Barbara Porton, Adriana Ferreira, Lynn E. DeLisi, Hung Teh Kao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background Synapsin III plays a role in neuronal plasticity and maps to chromosome 22q12-13, a region suggested to be linked to schizophrenia. To determine if synapsin III plays a role in this disease, we searched for polymorphisms in this gene in patients with schizophrenia and controls. Methods The synapsin III gene was initially sequenced from 10 individuals with schizophrenia to identify polymorphisms. Association analysis was then performed using 118 individuals with schizophrenia and 330 population controls. Synapsin III expression was studied by immunoblot analyses, and phosphorylation sites were mapped by sequencing trypsin-digested synapsin III fragments phosphorylated with phosphorus-32. Results A rare, missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia than in controls (p = .0048). The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. Phosphorylation at Ser470 was increased during neonatal development and in response to neurotrophin-3 in cultured hippocampal neurons. Conclusions Our observations suggest an association of a rare polymorphism in synapsin III with schizophrenia, but further studies will be required to clarify its role in this disease.

Original languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalBiological psychiatry
Volume55
Issue number2
DOIs
StatePublished - Jan 15 2004

Funding

This work was supported by U.S. Public Health Service Grants MH444245 (LED), MH60496-01 (H-TK; John Rotrosen, M.D., principal investigator), and Axys Pharmaceuticals (LED). BP is a 2000 Katowitz-Radin Investigator of the National Alliance for Research in Schizophrenia and Affective Disorders. The catalytic subunit of PKA was a gift from Angus Nairn and Atsuko Horiuchi, and cdk5 was a gift from Yong Kim. We thank Timothy J. Crow and Rekha Wadekar for provision of some DNA samples.

Keywords

  • Candidate genes
  • Mitogen-activated protein kinase
  • Neurotrophin
  • Phosphorylation
  • Signal transduction

ASJC Scopus subject areas

  • Biological Psychiatry

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