Apoptosis is an important mode of programmed cell death in which cells are eliminated rapidly without inflicting immune response. Apoptosis is essential for homeostasis and embryonic development, while abnormal apoptosis is associated with various diseases. PICK1 (protein interacting with C kinase 1) is a peripheral membrane protein containing a PDZ domain and a BAR domain. It regulates the subcellular distribution and expression of its PDZ-binding partners in nervous system and other tissues. The interactions of BAR domain participate in PICK1’s function including AMPA receptor trafficking, insulin processing and spermiogenesis.

In this study, the cleavage of PICK1 at C-terminal acid region during apoptosis was identified with induction of Staurosporine or overexpression of Fas ligand...[ Read more ]

Apoptosis is an important mode of programmed cell death in which cells are eliminated rapidly without inflicting immune response. Apoptosis is essential for homeostasis and embryonic development, while abnormal apoptosis is associated with various diseases. PICK1 (protein interacting with C kinase 1) is a peripheral membrane protein containing a PDZ domain and a BAR domain. It regulates the subcellular distribution and expression of its PDZ-binding partners in nervous system and other tissues. The interactions of BAR domain participate in PICK1’s function including AMPA receptor trafficking, insulin processing and spermiogenesis.

In this study, the cleavage of PICK1 at C-terminal acid region during apoptosis was identified with induction of Staurosporine or overexpression of Fas ligand. The truncated PICK1 decreased interaction with ICA69, a PICK1 binding partner involved in mediating the regulatory role of PICK1 in AMPA receptor trafficking. Distinct from the full length PICK1, the truncation could form clusters with ICA69 in HEK293T cells. Although the cleaved PICK1 alone showed no effect on the interaction and distribution of GluA2, when expressed with ICA69, the truncated PICK1 elevated binding with GluA2 and redistributed GluA2 in clusters. Moreover, the cleavage of PICK1 enhanced GluA2 surface expression in the presence of ICA69. These results suggested that GluA2 trafficking may be affected during apoptosis with the cleavage of PICK1.