Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (hDAT R51W) in dopamine neurotransmission and behaviors.

Background: Syntaxin 1 (STX1) is a presynaptic plasma membrane protein that coordinates synaptic vesicle fusion. STX1 also regulates the function of neurotransmitter transporters, including the dopamine (DA) transporter (DAT). The DAT is a membrane protein that controls DA homeostasis through the high-affinity re-uptake of synaptically released DA.

Deficits in syntaxin 1 phosphorylation in schizophrenia prefrontal cortex.

Background: Schizophrenia has been described as a disease of the synapse. On the basis of previous studies reporting reductions in the levels and activity of CK2 (also know as casein kinase 2 or II) in the brain of subjects with schizophrenia, we hypothesized that CK2-mediated phosphorylation of the presynaptic protein syntaxin 1 (Stx 1) is deficient in schizophrenia. This in turn could affect the binding of Stx 1 to its protein partners and result in abnormal neurotransmitter release and synaptic transmission.