Alternative titles; symbols
HGNC Approved Gene Symbol: PICK1
Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38) : 22:38,057,255-38,075,701 (from NCBI)
Staudinger et al. (1995) obtained a mouse cDNA encoding Prkcabp, which they called Pick1 (protein interacting with C kinase-1), using a yeast 2-hybrid screen with the catalytic domain of the alpha isoform of activated protein kinase C (PRKCA; 176960) as bait. Immunofluorescence microscopy demonstrated intense perinuclear and diffuse cytoplasmic staining.
Using a yeast 2-hybrid screen of a B-cell cDNA library with p67-phox (NCF2; 233710) as bait, Takeya et al. (2000) obtained a cDNA encoding human PRKCABP, which they called PICK1. Sequence analysis predicted that the 415-amino acid protein, which is 92% identical to the mouse protein, contains an N-terminal PDZ domain and a conserved arfaptin homology (AH) domain (see 601638). Northern blot analysis revealed ubiquitous expression of a 2.0-kb PICK1 transcript.
Using yeast 2-hybrid analysis, Takeya et al. (2000) found that the PDZ domain of PICK1, but not the AH domain, interacts with the C termini of the GTP-bound forms of ADP-ribosylation factor-1 (ARF1; 103180) and ARF3 (103190). The interaction with ARF5 (103188) and ARF6 (600464) was weak, suggesting that the PICK1 interaction is specific for class I ARFs and that it may regulate Golgi-to-endoplasmic reticulum vesicle transport.
Dev et al. (1999) showed that the PDZ domain of rat Pick1 interacts with the last 10 amino acids of the short C-terminal alternative splice variants of AMPA receptor (AMPAR) subunits (e.g., GLUR2; 138248). They proposed that E-S-V/I-K-I, a sequence found in these 10 amino acids, is a novel PDZ-binding motif. Dev et al. (1999) noted that PRKCA phosphorylates Pick1 efficiently but binds Pick1 in both the phosphorylated and unphosphorylated states.
Xia et al. (1999) reported that Pick1 interacts with mouse AMPA glutamate receptors and noted their colocalization at excitatory synapses in the brain.
Using a yeast 2-hybrid system, Cowan et al. (2000) demonstrated that mouse Pick1 binds the C-terminal tail of Ephb2 (600997).
Metabotropic glutamate receptor-7 (mGluR7; 604101) localizes specifically to presynaptic active zones. Boudin et al. (2000) showed that the extreme C-terminal 3 amino acids of mGluR7 interact with the PDZ domain of Pick1. Immunofluorescence microscopy demonstrated that both proteins are localized at excitatory synapses in hippocampal neurons. The authors showed that the clustering of mGluR7 at synapses requires its C-terminal PDZ-binding residues. Mutant mGluR7 lacking the PDZ-binding residues localized diffusely along axons rather than at the synapse, suggesting a role for Pick1 as a scaffolding molecule at presynaptic sites.
At rat cerebellar parallel fiber-stellate cell synapses, Ca(2+) influx through Glur2-lacking AMPARs drives incorporation of Ca(2+)-impermeable Glur2-containing AMPARs, generating rapid changes in excitatory postsynaptic current properties. Liu and Cull-Candy (2005) found that repetitive synaptic activity triggered loss of Ca(2+)-permeable AMPARs by disrupting their interaction with Grip (GRIP1; 604597). Pick drove activity-dependent delivery of Ca(2+)-impermeable receptors into the synaptic membrane. Liu and Cull-Candy (2005) concluded that dynamic regulation of AMPARs by GRIP and PICK provides a mechanism for controlling Ca(2+) permeability of synaptic receptors.
Takeya et al. (2000) determined that the PICK1 gene contains 13 exons and spans at least 18 kb.
By its inclusion within a mapped clone, Takeya et al. (2000) mapped the PICK1 gene to 22q12.3-q13.2.
Steinberg et al. (2006) generated 2 lines of transgenic mice: Pick1-null mice and those with targeted disruption of the C-terminal PDZ ligand of GluR2 (GRIA2; 138247), a binding site of GluR2 to Pick1. Purkinje cells and cerebellar slices from both groups of mutant mice showed absence of cerebellar long-term depression (LTD). Rescue studies showed that the PDZ and the BAR domains of Pick1 were required for LTD. Phosphorylation at ser880 of GluR2 was also required for cerebellar LTD as well as for proper GluR2 trafficking. Overall, the results indicated that Pick1-GluR2 PDZ-based interactions and GluR2 phosphorylation are required for cerebellar LTD expression in mice.
Xiao et al. (2009) found that Pick1 -/- mice appeared grossly normal, but that male Pick1 -/-mice were completely infertile and had a phenotype resembling human globozoospermia (see 102530). Testis of Pick1 -/- mice showed fragmentation of acrosomes in early stages of spermiogenesis and increased apoptosis in seminiferous tubules. Acrosome fragmentation was followed by defects in nuclear elongation and mitochondrial sheath formation, leading to round-headed sperm, reduced sperm count, and severely impaired sperm motility. Wildtype Pick1 interacted with Gopc (606845) and Ck2-alpha-prime (CSNK2A2; 115442), proteins whose deficiencies lead to globozoospermia in mice. Pick1 was highly expressed in round spermatids and localized to Golgi-derived proacrosomal granules. Gopc colocalized with Pick1 in the Golgi region and facilitated formation of Pick1-positive clusters. Xiao et al. (2009) concluded that PICK1 is involved in vesicle trafficking from the Golgi to the acrosome and cooperates with GOPC and CK2-alpha-prime in acrosome biogenesis.
Boudin, H., Doan, A., Xia, J., Shigemoto, R., Huganir, R. L., Worley, P., Craig, A. M. Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site. Neuron 28: 485-497, 2000. [PubMed: 11144358] [Full Text: https://doi.org/10.1016/s0896-6273(00)00127-6]
Cowan, C. A., Yokoyama, N., Bianchi, L. M., Henkemeyer, M., Fritzsch, B. EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron 26: 417-430, 2000. [PubMed: 10839360] [Full Text: https://doi.org/10.1016/s0896-6273(00)81174-5]
Dev, K. K., Nishimune, A., Henley, J. M., Nakanishi, S. The protein kinase C-alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology 38: 635-644, 1999. [PubMed: 10340301] [Full Text: https://doi.org/10.1016/s0028-3908(98)00230-5]
Liu, S. J., Cull-Candy, S. G. Subunit interaction with PICK and GRIP controls Ca(2+) permeability of AMPARs at cerebellar synapses. Nature Neurosci. 8: 768-775, 2005. [PubMed: 15895086] [Full Text: https://doi.org/10.1038/nn1468]
Staudinger, J., Zhou, J., Burgess, R., Elledge, S. J., Olson, E. N. PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system. J. Cell Biol. 128: 263-271, 1995. [PubMed: 7844141] [Full Text: https://doi.org/10.1083/jcb.128.3.263]
Steinberg, J. P., Takamiya, K., Shen, Y., Xia, J., Rubio, M. E., Yu, S., Jin, W., Thomas, G. M., Linden, D. J., Huganir, R. L. Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron 49: 845-860, 2006. [PubMed: 16543133] [Full Text: https://doi.org/10.1016/j.neuron.2006.02.025]
Takeya, R., Takeshige, K., Sumimoto, H. Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors. Biochem. Biophys. Res. Commun. 267: 149-155, 2000. [PubMed: 10623590] [Full Text: https://doi.org/10.1006/bbrc.1999.1932]
Xia, J., Zhang, X., Staudinger, J., Huganir, R. L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22: 179-187, 1999. [PubMed: 10027300] [Full Text: https://doi.org/10.1016/s0896-6273(00)80689-3]
Xiao, N., Kam, C., Shen, C., Jin, W., Wang, J., Lee, K. M., Jiang, L., Xia, J. PICK1 deficiency causes male infertility in mice by disrupting acrosome formation. J. Clin. Invest. 119: 802-812, 2009. [PubMed: 19258705] [Full Text: https://doi.org/10.1172/JCI36230]