Pacsin 3 (also known as Syndapin 3) is a member of the highly conserved Pacsin protein sub-family which constitutes a branch of the larger F-BAR domain protein family.

Pacsin 3, as well as other members of its family, is a cytoplasmic protein involved in receptor-mediated endocytosis, synaptic vesicle trafficking and biogenesis of different cellular organelles and is mostly, but not only, expressed in lung and muscle tissues. Pacsin 3 contains an N-terminal F-BAR domain and a C-terminal mono-Src homology 3 domain¹.

The C-terminal SH3 domain of Pacsin 3 interacts with the N-terminal proline-rich domain of TRPV4 at residues 132-144 and enhances the cell surface expression of TRPV4, probably through the inhibition of the endocytotic process². The SH3 domain is also responsible for interactions with the protein dynamin and with N-WASP, a potent activator of the Arp2/3 complex F-actin-nucleation machine³. Pacsin’s interaction with dynamin contributes to fusion pore expansion in chromaffin cells in the adrenal medulla. Pacsin-dynamin interaction occurs through an SH3-PRD binding interaction that depends on the central proline residue in the ligand-binding site of Pacsin’s SH3 domain⁴.

Pacsin 3 is also involved in the trafficking of AMPA receptors in neurons through its interaction with PICK1 (Protein interacting with C-kinase 1). PICK1 and Pacsin 3 form a complex with the C-termini of the AMPA subunits GluA2 and GluA3. This interaction between Pacsin 3 and PICK1 is regulated by Pacsin phosphorylation and is required for NMDA induced AMPA receptor endocytosis and cerebellar long term synaptic depression⁵.