Synaptojanin-1 was originally identified as one of the major Grb2-binding proteins that may participate in synaptic vesicle endocytosis []. It also acts as an Src homology 3 (SH3) domain-binding brain-specific inositol 5-phosphatase, with a putative role in clathrin-mediated endocytosis [, ]. Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p [], a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2 []. Synaptojanin-1 has two tissue-specific alternative splicing isoforms, synaptojanin-145 expressed in brain and synaptojanin-170 expressed in peripheral tissues. Synaptojanin-145 is very abundant in nerve terminals and may play an essential role in the clathrin-mediated endocytosis of synaptic vesicles []. In contrast to synaptojanin-145, synaptojanin-170 contains three unique asparagine-proline-phenylalanine (NPF) motifs in the C-terminal region, and may function as a potential binding partner for Eps15, a clathrin coat-associated protein acting as a majorsubstrate for the tyrosine kinase activity of the epidermal growth factor receptor [].
