Function
Intersectin (ITSN) is an endocytic multidomain scaffold protein in neurons and is important regulator of synaptic vescicles replenishment at hippocampal synapses. The replenishment is needed in order to sustain neurotransmission during periods of elevated activity. ITSN interacts with synapsin I through its SH3 domains[1].
ITSN 2 is also involved in clathrin-mediated endocytosis and is very similar to ITSN 1.
ITSN-1 has two isoforms as a result of differential splicing:
- ITSN-1 short form is 140kD and expressed in all tissues
- ITSN-1 long form is 200kD and expressed in neutrons, eye, heart, blood cells and kidney[2].
- ITSN-2 short form contains 2 EH domains, a coiled-coil domain and 5 SH3 domains
- ITSN-2 long formcontains an extra carboxylate domain[3].
Relevance
ITSN 1 is expressed in neuroblastoma tumors and tumor cell lines and is necessary for their tumorigenic properties[4].
ITSN 2 might be a potential biomarker for discrimination of severe acute pancreatitis to improve the prognosis of patients[5]. Overexpression of ITSN 1 is implicated for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease[6].
Structural highlights
The 3D structure of shows extensive contact surface composed mainly of hydrophobic interactions[7].
