TY - JOUR
T1 - A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III
T2 - Possible relationship to schizophrenia
AU - Porton, Barbara
AU - Ferreira, Adriana
AU - DeLisi, Lynn E.
AU - Kao, Hung Teh
N1 - Funding Information:
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.
PY - 2004/1/15
Y1 - 2004/1/15
N2 - 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.
AB - 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.
KW - Candidate genes
KW - Mitogen-activated protein kinase
KW - Neurotrophin
KW - Phosphorylation
KW - Signal transduction
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U2 - 10.1016/j.biopsych.2003.07.002
DO - 10.1016/j.biopsych.2003.07.002
M3 - Article
C2 - 14732590
AN - SCOPUS:1442284208
SN - 0006-3223
VL - 55
SP - 118
EP - 125
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 2
ER -