Disease relevance of SCIN

• Adseverin was produced in Escherichia coli and purified to homogeneity [1].
• The plasma membrane of Mycoplasma mycoides subsp. mycoides SC (strain KH3J) contains over 160 polypeptides with apparent molecular masses ranging from 14 to 125 kDa and isoelectric point values (pIs) from 5 to 9 [2].

High impact information on SCIN

• Recombinant scinderin enhances exocytosis, an effect blocked by two scinderin-derived actin-binding peptides and PIP2 [3].
• PIP2 effect was blocked by peptide Sc-PIP2BP (with sequence corresponding to a PIP2-binding site of scinderin) [3].
• The presence of gelsolin and scinderin, two Ca(2+)-dependent actin filament severing proteins, in the cortical surface of the chromaffin cells, suggests the possibility that cell stimulation brings about activation of one or more actin filament severing proteins with the consequent disruption of actin networks [4].
• Cortical filamentous actin disassembly and scinderin redistribution during chromaffin cell stimulation precede exocytosis, a phenomenon not exhibited by gelsolin [4].
• Scinderin, a novel Ca2+-activated actin filament-severing protein, has been purified to homogeneity from bovine adrenal medulla using a combination of several chromatographic procedures [5].

Biological context of SCIN

• The observation strongly suggested that adseverin is not involved in secretory processes in general but is specifically involved in exocytosis [1].
• A new member of the gelsolin/villin family of actin regulatory proteins was initially identified by screening an adult murine brain cDNA library with a probe for bovine adseverin [6].
• Sc domain role in secretion was studied by co-transfection of human growth hormone (hGH) reporter gene and green fluorescent protein (GFP)-fusion Sc constructs [7].
• In addition, scinderin antisense treatment did not alter the expression of proteins involved in vesicle-plasma membrane fusion, such as synaptophysin, synaptotagmin or syntaxin, indicating a lack of effects on the fusion machinery components [8].
• In view of the wide tissue distribution of gelsolin, another actin filament-severing protein, experiments were performed to determine the tissue expression of scinderin [9].

Anatomical context of SCIN

• To understand how adseverin can sever actin filaments, we identified the actin-binding domains [10].
• In situ hybridization demonstrated that adseverin mRNA was differentially expressed in the bovine adrenal gland; it was expressed in the adrenal medulla but not in most parts of the adrenal cortex, although both have a secretory function [1].
• Adseverin is a Ca(2+)-dependent actin filament-severing protein that is presumed to have a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane [1].
• Differential expression of bovine adseverin in adrenal gland revealed by in situ hybridization. Cloning of a cDNA for adseverin [1].
• Chromaffin cell scinderin, a novel calcium-dependent actin filament-severing protein [5].

Associations of SCIN with chemical compounds

• The NH2 termini of native adseverin and the Mr 42,000 fragment were confirmed to be blocked by amino acid sequencing [10].
• Ca2(+)-dependent binding of adseverin to PS liposomes but not to PC or PE liposomes was observed by a centrifugation assay [11].
• A 74-kDa protein (adseverin) derived from adrenal medulla severs actin filaments and nucleates actin polymerization in a Ca2(+)-dependent manner but does not form an EGTA-resistant complex with actin monomers, which is different from the gelsolin-actin interaction [11].
• Histamine evoked similar patterns of distribution of scinderin and filamentous actin [12].
• The trigger for the release of Ca2+ was inositol 1,4,5-trisphosphate because U-73122, a phospholipase C inhibitor, but not its inactive isomer (U-73343), inhibited the increases in IP3 and intracellular Ca2+ levels, scinderin redistribution, cortical F-actin disassembly, and catecholamine release in response to histamine [12].

Regulatory relationships of SCIN

• Here we report that histamine-H1 receptor activation induces redistribution of scinderin, a Ca(2+)-dependent F-actin severing protein, cortical F-actin disassembly, and catecholamine release [12].

Other interactions of SCIN

• 2) Adseverin belonged to the gelsolin family of proteins, which consists of six homologous segments [1].
• Nucleotide and amino acid sequence analysis indicate that scinderin has six domains each containing three internal sequence motifs, two actin and two PIP2 binding sites and has 63 and 53% homology with gelsolin and villin [13].

Analytical, diagnostic and therapeutic context of SCIN

• Calcium sensitive actin severing protein, adseverin, with Mr 74,000, was cleaved into two fragments of Mr 42,000 and Mr 39,000 by V8 protease and trypsin, and both fragments were purified by high performance (pressure) liquid chromatography ion-exchange column chromatography [10].
• Immunoblotting tests with the same antibodies indicated that scinderin is also expressed in brain and anterior as well as posterior pituitary [5].
• Scinderin interacts with F-actin in the presence of Ca2+ and produces a decrease in the viscosity of actin gels as a result of F-actin filament severing as demonstrated by electron microscopy [5].
• Extracts prepared from different bovine tissues were tested by actin-DNase I Sepharose 4B-binding procedure and immunoprecipitation followed by immunoblotting with scinderin and gelsolin antibodies [9].
• Molecular cloning and functional expression of chromaffin cell scinderin indicates that it belongs to the family of Ca(2+)-dependent F-actin severing proteins [13].

References