Table I. Proteins that interact with PICK1 but for which there is no or only weak evidence^a.

Putative targets and models of schizophrenia	PICK1 interaction?	Refs
Receptors and transporters
Glu receptors: reduced NMDA receptor activity and glutamate release is associated with schizophrenia; NMDA receptor activators and glycine-site modulators limit symptoms	Yes – PICK1 binds to many Glu receptors	b
Dopamine receptors and transporters: increased D2 receptor expression and dopamine release in the striatum is linked to schizophrenia; D2 receptor antagonism reduces psychosis	Yes – PICK1 interacts with DAT	b
ErbB receptors and NRG: NRG expression is altered in schizophrenia; NRG is found in glutamate- containing vesicles; NRG binds to ErbB receptors and alters NMDA receptor expression	Yes – PICK1 binds to ErbB receptors	[5,6]
5-HT receptors: the hypersensitivity of 5-HT receptors is linked to schizophrenia; 5-HT2A receptor antagonism reduces symptoms of schizophrenia	Unknown – interaction not investigated	[63,64]
GABA receptors: a lack of inhibitory GABA tone probably occurs in schizophrenia because of altered glutamate activity	Unknown – interaction not investigated	[65,66]
Nicotinic acetylcholine receptors: promoter variants and SNPs in the nicotinic α7 receptor are associated with schizophrenia	Unknown – interaction not investigated	[67,68]
Other synaptic proteins
SNAP-25: schizophrenia might be associated with abnormal levels of protein in presynaptic terminals and the SNARE complex, which is involved in vesicle docking	Yes – PICK1 interacts with β-SNAP and NSF	[69-72]
Dysbindin: altered expression and SNPs are linked to schizophrenia; dysbindin is a presynaptic protein that binds to dystrobrevin, and regulates synaptic structures and glutamate release	Linked via glutamate receptors?	[5,6]
RGS4: decreased expression and SNPs are associated with schizophrenia; RGS4 is a negative regulator of mGlu receptors	Linked via glutamate receptors?	[5,6]
Enzyme dysfunction and transmitter metabolism
d-serine metabolism: d-serine activates the NMDA receptor glycine site; it is synthesized by SR and degraded by DAAO–G72; d-serine treatment ameliorates schizophrenia	Yes – PICK1 binds to SR	b
COMT: COMT controls dopamine levels; SNPs in this enzyme are associated with schizophrenia	Linked via DAT?	[5,6]
Brain development abnormalities and viral infections
Coxsackie and adenovirus receptor: viral infections of Coxsackie B5 during the newborn period might increase the risk of schizophrenia	Yes – PICK1 interacts with CAR	[73,74]
Neurotrophic factors: low expression levels of NGF and SNPs of BDNF might alter neuronal development; atypical antipsychotics and AMPA receptor modulators release BDNF	Yes – BDNF regulates PICK1 expression	[75-78]
Inflammatory cytokines: increased release of cytokines during problems with birth, and fetal viral infections might be associated with increased risk of schizophrenia	Unknown – can PICK1 alter cytokine release?	[79,80]

^aAbbreviations: NGF, nerve growth factor; SNAP, soluble NSF attachment protein; SNARE, SNAP receptor.

^bSee main text.