Disease relevance of ITSN1

• Intersectin-1 (ITSN1) and Down syndrome candidate region 1 (DSCR1) are two such genes [1].
• CONCLUSIONS: These results suggest that ITSNP is a safe and potentially effective treatment for established DCV and cerebral ischemia refractory to conventional treatment [2].

Psychiatry related information on ITSN1

• Alzheimer's disease and endocytic dysfunction: Clues from the Down syndrome-related proteins, DSCR1 and ITSN1 [1].

High impact information on ITSN1

• Two others, intersectin and syndapin, bind N-WASp, a potent activator of actin assembly via the Arp2/3 complex [3].
• In particular, I discuss the relationship between actin and three components of the endocytic machinery--dynamin, HIPs (huntingtin-interacting proteins) and intersectin [4].
• Using PC12 and chromaffin cells, we now show the presence of intersectin-1 at exocytotic sites [5].
• Thus, we observed that intersectin, syndapin, and mAbp1, which are necessary for the uptake of transferrin (Tf), a marker of the clathrin route, are not required for gammac receptor endocytosis [6].
• These results suggest that intersectin functions in cell signaling in addition to its role in endocytosis and may link these cellular processes [7].

Chemical compound and disease context of ITSN1

• We trapped an exon of DSCR1 (Down Syndrome Candidate Region 1) and two different exons of a gene called human Intersectin (ITSN) [8].

Biological context of ITSN1

• Intersectin 1 (ITSN1) is a binding partner of dynamin that has been shown to participate in clathrin-mediated endocytosis [9].
• Here we report 7 novel splice variants of the human and mouse ITSN1 genes and demonstrate conservation of alternative splicing affecting SH3A and SH3C in mouse [10].
• The structure of the human ITSN protein is consistent with its involvement in membrane-associated molecular trafficking and signal transduction pathways [11].
• Finally, affinity selection experiments with the SH3 domains of Intersectin identified two endocytic proteins, dynamin and synaptojanin, as potential interacting proteins [12].
• Using fluorescence resonant energy transfer analysis, we demonstrate that ITSN complexes with Ras in living cells leading to Ras activation on intracellular vesicles [13].

Anatomical context of ITSN1

• Taken together, the results indicate the crucial role of intersectin in the mechanism of caveolae fission in endothelial cells [14].
• Intersectin regulates fission and internalization of caveolae in endothelial cells [14].
• A cell-free system depleted of intersectin failed to support caveolae fission from the plasma membrane [14].
• These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2 [15].
• We now show that the NPF repeats of SCAMP1 bind to two EH domain proteins, intersectin 1, which is involved in endocytic budding at the plasma membrane, and gamma-synergin, which may mediate the budding of vesicles in the trans-Golgi complex [16].

Associations of ITSN1 with chemical compounds

• A biotin assay used to quantify caveolae internalization and extensive EM morphological analysis of ECs overexpressing wt-intersectin indicated a wide range of morphological changes (i.e., large caveolae clusters marginated at cell periphery and pleiomorphic caveolar necks) as well as impaired caveolae internalization [14].
• We demonstrate herein by coimmunoprecipitation, velocity sedimentation on glycerol gradients, and cross-linking that intersectin is present in ECs in a membrane-associated protein complex containing dynamin and SNAP-23 [14].
• More recently, we identified mammalian Sos, a guanine-nucleotide exchange factor for Ras, as an intersectin SH3 domain-binding partner [17].
• And finally, intersectin cooperated with progesterone to accelerate maturation of Xenopus laevis oocytes [18].
• Likewise, GEF activity afforded by DH/PH fragments of intersectin and Dbs are also not altered by phosphoinositide interactions [19].

Regulatory relationships of ITSN1

• Overexpression of the SH3 domains of intersectin blocks transferrin receptor endocytosis, possibly by disrupting targeting of accessory proteins of clathrin-coated pit formation [17].
• Our data suggest that intersectin controls the amount of dynamin released from the synaptic vesicle cluster to the periactive zone and that it may regulate fission of clathrin-coated intermediates [20].

Other interactions of ITSN1

• Here we report the characterization of a new human gene, ITSN2, highly similar to ITSN1 [9].
• Moreover, their overexpression, as well as the corresponding ITSN1 protein forms, inhibits transferrin internalization [9].
• We also showed that intersectin interaction with dynamin was important in regulating the fission and internalization of caveolae [14].
• Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2 [15].
• Here, analysis of 21q22.1-->q22.2 genomic sequence revealed that ITSN consists of 41 exons spanning approximately 250 kb and maps between GART and D21S325 [21].

Analytical, diagnostic and therapeutic context of ITSN1

• Electron microscopy (EM) immunogold labeling studies indicated that intersectin associated preferentially with the caveolar necks, and it remained associated with caveolae after their fission from the plasmalemma [14].
• By Alu-splice PCR we have trapped two exons and subsequently identified the full length cDNA of a human gene, Intersectin (ITSN), which maps to chromosome 21q22.1 between markers D21S320 and D21S325 [22].
• Post-embedding immunocytochemistry demonstrated that proteins involved in synaptic vesicle recycling, including dynamin, intersectin, and synapsin, occur at higher levels (labeling per vesicle) in tonic dorsal column synapses than in phasic reticulospinal synapses [23].
• Acute perturbation of the intersectin-dynamin interaction by microinjection of either intersectin antibodies or Src homology 3 (SH3) domains inhibited endocytosis at the fission step [20].

References