Protein interacting with C kinase 1 (PICK1) is a higly conserved peripheral membrane protein involved in protein trafficking, a function that has been well characterized in neurons. PICK1 contains an N-terminal PDZ (PSD-95/Dlg/ZO-1) domain, which is known to mediate protein – protein interaction; a central BAR (Bin/amphiphysin/Rvs) domain, which is known to be homologous to the BAR domain of arfaptin 2 and binds to negatively charged lipid; and an acidic C terminus. Our lab has proposed the model that the PDZ domain of PICK1 binds to the cargo proteins, sorting the cargo proteins to specific vesicle complex; while the BAR domain of PICK1 binds to the lipid membrane structure and facilitates the formation of vesicle....[ Read more ]

Protein interacting with C kinase 1 (PICK1) is a higly conserved peripheral membrane protein involved in protein trafficking, a function that has been well characterized in neurons. PICK1 contains an N-terminal PDZ (PSD-95/Dlg/ZO-1) domain, which is known to mediate protein – protein interaction; a central BAR (Bin/amphiphysin/Rvs) domain, which is known to be homologous to the BAR domain of arfaptin 2 and binds to negatively charged lipid; and an acidic C terminus. Our lab has proposed the model that the PDZ domain of PICK1 binds to the cargo proteins, sorting the cargo proteins to specific vesicle complex; while the BAR domain of PICK1 binds to the lipid membrane structure and facilitates the formation of vesicle.

Here, we report that male mice deficient in PICK1 are infertile and have a phenotype resembling the human disease globozoospermia. The primary defect in the testes of Pick1-knockout mice was fragmentation of acrosomes in the early stages of spermiogenesis. This 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. We found that PICK1 interacted with Golgi-associated PDZ- and coiled-coil motif–containing protein and the primary catalytic subunit of protein kinase 2 (CK2α′), 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. Furthermore, there was an increase in apoptosis in the seminiferous tubules of Pick1–/– mice, a phenotype also seen in CK2α′-deficient mice. Our results suggest that PICK1 is involved in vesicle trafficking from the Golgi apparatus to the acrosome and cooperates with other proteins such as GOPC and CK2α′ in acrosome biogenesis.