Topic
Intersectin 2
About: Intersectin 2 is a research topic. Over the lifetime, 23 publications have been published within this topic receiving 917 citations. The topic is also known as: PRO2015 & SH3D1B.
Papers
TL;DR: Intersectin 2 appears to function cooperatively with WASp and cdc42 to link the clathrin endocytic machinery to WASp-mediated actin polymerization and ultimately to occupancy-induced TCR endocytosis.
Abstract: Induction of T cell antigen receptor (TCR) endocytosis has a significant impact on TCR signaling and T cell behavior, but the molecular interactions coordinating internalization of the activated TCR are poorly understood. Previously we have shown that TCR endocytosis is regulated by the Wiskott Aldrich Syndrome protein (WASp), a cytosolic effector which, upon interaction with the cdc42 Rho GTPase, couples TCR engagement to Arp 2/3 complex-mediated actin polymerization. Here we report that WASp associates in T cells with intersectin 2, an endocytic adaptor containing multiple domains including a Dbl homology (DH) domain with the potential to activate Rho GTPases. Intersectin 2 association with WASp increases after TCR engagement, and its overexpression in Cos-7 cells induces WASp translocation to endocytic vesicles within which intersectin 2 colocalizes with both WASp and cdc42. Intersectin 2, but not a DH domain-deleted (ΔDH) form of intersectin 2, and stimulation via the TCR also trigger the activation of cdc42. Induction of TCR internalization is also augmented by intersectin 2 and severely impaired by latrunculin B treatment. Thus, intersection 2 appears to function cooperatively with WASp and cdc42 to link the clathrin endocytic machinery to WASp-mediated actin polymerization and ultimately to occupancy-induced TCR endocytosis.
148 citations
TL;DR: In this article, the authors report the characterization of a new human gene, ITSN2, highly similar to ITSN1, which can act as a guanine nucleotide exchange factor for Rho-like GTPases.
95 citations
TL;DR: It is shown that only exosomes expressing a Tspan8-CD49d complex preferentially bind endothelial cells, which initiates angiogenesis and initiates tetraspanin-web rearrangements, which have strong functional consequences for the cell, exosome-delivery andExosome target selection.
85 citations
TL;DR: It is concluded that, in contrast with schizophrenia, common ROHs are rarely associated with susceptibility to bipolar disorder, and this supports the idea that predominantly different genes are increasing susceptibility to schizophrenia and bipolar affective disorders.
Abstract: Background Recent studies have reported large common regions of homozygosity (ROHs) that are the result of autozygosity, that is, the cooccurrence within individuals of long haplotypes that have a high frequency in the population. A recent study reports that such regions are found more commonly in individuals with schizophrenia compared with controls, and identified nine ‘risk ROHs’ that were individually more common in cases. Of these, four contained or neighboured genes associated with schizophrenia (NOS1AP/UHMK1, ATF2, NSF and PIK3C3). Methods We have applied the same methodology to a UK sample of 506 cases with bipolar disorder and 510 controls. Results There was no overall excess of common ROHs among bipolar individuals. With one exception, the haplotypes accounting for the ROHs appeared to be distributed according to the Hardy–Weinberg equilibrium. One ROH was individually more common among cases (uncorrected P = 0.0003). This ROH spanned the chromosome 2p23.3 gene ITSN2 (the gene for intersectin 2 isoform 2). However, inspection of the homozygous haplotypes and haplotype-based tests for association failed to provide a clearer understanding of why this ROH was occurring more commonly. Conclusion Overall, we conclude that, in contrast with schizophrenia, common ROHs are rarely associated with susceptibility to bipolar disorder. This supports the idea that predominantly different genes are increasing susceptibility to schizophrenia and bipolar affective disorders.
40 citations
TL;DR: It is demonstrated that expression of a miR cluster mmu‐miR‐23–24–27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo, and this findings reinforce a role for miRs in a Aldosterone regulation of Na+ transport, and implicate miR‐27 in ald testosterone's action via a novel target.
Abstract: The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na(+) ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na(+) regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23∼24∼27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo. Increasing the expression of these miRs increased Na(+) transport in the absence of aldosterone stimulation. Potential miR targets were evaluated and miR-27a/b was verified to bind to the 3'-untranslated region of intersectin-2, a multi-domain protein expressed in the distal kidney nephron and involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and protein was decreased after aldosterone stimulation. Depletion of Itsn2 expression, mimicking aldosterone regulation, increased ENaC-mediated Na(+) transport, while Itsn2 overexpression reduced ENaC's function. These findings reinforce a role for miRs in aldosterone regulation of Na(+) transport, and implicate miR-27 in aldosterone's action via a novel target. This article is protected by copyright. All rights reserved.
23 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 1 |
| 2020 | 1 |
| 2019 | 3 |
| 2018 | 1 |
| 2017 | 3 |
| 2015 | 1 |