title: Emerging roles for intersectin (ITSN) in regulating signaling and disease pathways.
abstract: Intersectins (ITSNs) represent a family of multi-domain adaptor proteins that regulate endocytosis and cell signaling. ITSN genes are highly conserved and present in all metazoan genomes examined thus far. Lower eukaryotes have only one ITSN gene, whereas higher eukaryotes have two ITSN genes. ITSN was first identified as an endocytic scaffold protein, and numerous studies reveal a conserved role for ITSN in endocytosis. Subsequently, ITSNs were found to regulate multiple signaling pathways including receptor tyrosine kinases (RTKs), GTPases, and phosphatidylinositol 3-kinase Class 2beta (PI3KC2β). ITSN has also been implicated in diseases such as Down Syndrome (DS), Alzheimer Disease (AD), and other neurodegenerative disorders. This review summarizes the evolutionary conservation of ITSN, the latest research on the role of ITSN in endocytosis, the emerging roles of ITSN in regulating cell signaling pathways, and the involvement of ITSN in human diseases such as DS, AD, and cancer.
authors.affiliation: Department of Pharmacology, University of Illinois Cancer Center, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL 60612, USA. obryanj@uic.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hunter
authors.forename: Angela
authors.initials: A
authors.lastname: Russo
authors.forename: John P
authors.initials: JP
authors.lastname: O'Bryan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D058541:Class II Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C115919:intersectin 1; D058541:Class II Phosphatidylinositol 3-Kinases; C502616:PIK3C2B protein, human; D020794:Receptor Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases