人脑生长抑素相互作用组：SST 选择性地与 P 型家族 ATP 酶结合。
The human brain somatostatin interactome: SST binds selectively to P-type family ATPases.
机构信息
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Centre, Toronto, Ontario, Canada.
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
出版信息
PLoS One. 2019 May 28;14(5):e0217392. doi: 10.1371/journal.pone.0217392. eCollection 2019.
Somatostatin (SST) is a cyclic peptide that is understood to inhibit the release of hormones and neurotransmitters from a variety of cells by binding to one of five canonical G protein-coupled SST receptors (SSTR1 to SSTR5). Recently, SST was also observed to interact with the amyloid beta (Aβ) peptide and affect its aggregation kinetics, raising the possibility that it may bind other brain proteins. Here we report on an SST interactome analysis that made use of human brain extracts as biological source material and incorporated advanced mass spectrometry workflows for the relative quantitation of SST binding proteins. The analysis revealed SST to predominantly bind several members of the P-type family of ATPases. Subsequent validation experiments confirmed an interaction between SST and the sodium-potassium pump (Na+/K+-ATPase) and identified a tryptophan residue within SST as critical for binding. Functional analyses in three different cell lines indicated that SST might negatively modulate the K+ uptake rate of the Na+/K+-ATPase.
生长抑素（SST）是一种环状肽，通过与五种经典的 G 蛋白偶联 SST 受体（SSTR1 到 SSTR5）中的一种结合，被认为可以抑制多种细胞中激素和神经递质的释放。最近，人们还观察到 SST 与淀粉样β（Aβ）肽相互作用并影响其聚集动力学，这增加了它可能与其他脑蛋白结合的可能性。在这里，我们报告了一项 SST 相互作用组分析，该分析利用人脑提取物作为生物源材料，并采用先进的质谱工作流程进行 SST 结合蛋白的相对定量。该分析表明 SST 主要与 P 型家族的几种 ATP 酶结合。随后的验证实验证实了 SST 与钠钾泵（Na+/K+-ATPase）之间的相互作用，并确定 SST 内的一个色氨酸残基对结合至关重要。在三种不同的细胞系中的功能分析表明，SST 可能负调控 Na+/K+-ATPase 的 K+摄取率。
Zotero 插件