Role of PICK1 and ICA69 Complex in Protein Trafficking and Diseases
Jun Xia
Division of Life Science, Hong Kong University of Science and Technology
Mammalian cells are divided by elaborate membrane compartments. Proteins are
transported between different compartments via trafficking vesicles. Protein
trafficking is tightly regulated to ensure proper function of different
proteins. We identified PICK1, a peripheral membrane protein with a PDZ
domain and a BAR domain, as an important protein trafficking regulator. The
PDZ domain of PICK1 binds to a number of membrane proteins while the BAR
domain of PICK1 binds to liposome and couple membrane proteins to
trafficking vesicles. In addition, the BAR domain of PICK1 forms tight
heteromeric BAR domain complex with ICA69, another BAR domain containing
protein. The switch from heteromeric PICK1-ICA69 to homomeric PICK1-PICK1
BAR domain complex provides an important mechanism for vesicle sorting and
refinement. In brain, PICK1 interacts and regulates the trafficking of AMPA
type glutamate receptor and this regulation is critical to synaptic
plasticity, the cellular basis of learning and memory. In pancreatic beta-
cells, PICK1 controls the trafficking of insulin granules and its deficiency
leads to glucose intolerance and symptoms related to diabetes.