The protein interacting with C kinase 1 (PICK1) protein was first identified as a novel binding partner for protein kinase C. PICK1 contains a membrane-binding BAR domain and a PDZ domain interacting with many synaptic proteins, including AMPA receptor subunit GluA2 and the dopamine transporter. PICK1 is strongly implicated in GluA2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. However, several questions regarding the exact physiological and molecular functions of PICK1 remain, including its possible roles in other phenomena. The advantage of using C. elegans for research in neuroscience prompted us to look into PICK1's function genetically.

In this study, we have characterized PICK1's dual role in neuropeptid...[ Read more ]

The protein interacting with C kinase 1 (PICK1) protein was first identified as a novel binding partner for protein kinase C. PICK1 contains a membrane-binding BAR domain and a PDZ domain interacting with many synaptic proteins, including AMPA receptor subunit GluA2 and the dopamine transporter. PICK1 is strongly implicated in GluA2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. However, several questions regarding the exact physiological and molecular functions of PICK1 remain, including its possible roles in other phenomena. The advantage of using C. elegans for research in neuroscience prompted us to look into PICK1's function genetically.

In this study, we have characterized PICK1's dual role in neuropeptide signaling in C. elegans for the first time. Specifically, PICK1 functions together with its binding partners RIC-19 and UNC-108 to regulate DCV maturation in neuronal cell body. On the other hand, PICK1 targets to presynaptic site and negatively regulates the secretion of neuropeptide. Loss of PICK1 suppresses the DCV phenotypes of unc-31 mutants, indicating that PICK1 antagonizes UNC-31-dependent DCV release. Also, we propose that by interacting with GDP-bound RAB-3, PICK1 is required to maintain proper membrane/cytosol cycle of RAB-3 and negatively regulates neuropeptide release.