ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules
ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules
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DOI：
10.1002/j.1460-2075.1996.tb00564.x
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发表时间：
1996-05-01
期刊：
影响因子：
11.4
通讯作者：
Rabin, DU
中科院分区：
文献类型：
--
作者：
Solimena, M;Dirkx, R;Rabin, DU
胰岛细胞自身抗原（ICA）512是胰岛素依赖性糖尿病（IDDM）的一种新型自身抗原，与受体型蛋白酪氨酸磷酸酶（PTPases）同源。我们证明ICA 512是分泌颗粒的内在膜蛋白，在产生胰岛素的胰腺β细胞以及几乎所有其他分泌肽的内分泌细胞和含有神经分泌颗粒的神经元中表达。 ICA 512 在其腔域被裂解，暴露于细胞表面后，循环至高尔基复合体区域并被分选为新形成的分泌颗粒。通过免疫沉淀，在 15/17 (88%) 新诊断的 IDDM 患者中检测到抗 ICA 512 自身抗体，但在 10/10 的健康受试者中未检测到。这些结果表明酪氨酸磷酸化参与所有神经内分泌细胞共有的分泌颗粒功能的某些方面，并且IDDM中的自身抗体的子集针对含胰岛素颗粒的完整膜蛋白。
Islet cell autoantigen (ICA) 512 is a novel autoantigen of insulin-dependent diabetes mellitus (IDDM) which is homologous to receptor-type protein tyrosine phosphatases (PTPases). We show that ICA 512 is an intrinsic membrane protein of secretory granules expressed in insulin-producing pancreatic beta-cells as well as in virtually all other peptide-secreting endocrine cells and neurons containing neurosecretory granules. ICA 512 is cleaved at its luminal domain and, following exposure at the cell surface, recycles to the Golgi complex region and is sorted into newly formed secretory granules. By immunoprecipitation, anti-ICA 512 autoantibodies were detected in 15/17 (88%) newly diagnosed IDDM patients, but not in 10/10 healthy subjects. These results suggest that tyrosine phosphorylation participates in some aspect of secretory granule function common to all neuroendocrine cells and that a subset of autoantibodies in IDDM is directed against an integral membrane protein of insulin-containing granules.