The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms.
The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms.
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DOI：
10.3389/fendo.2013.00096
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发表时间：
2013-01-01
影响因子：
5.2
通讯作者：
Salton, Stephen R
中科院分区：
文献类型：
--
作者：
Lin, Wei-Jye;Salton, Stephen R
受调节的分泌途径提供对肽、生长因子和激素从神经内分泌和内分泌细胞以及神经元释放的关键控制，从而维持生理稳态。前肽和前激素被包装成致密核心颗粒（DCG），随着DCG成熟，它们经常在其中经历组织特异性加工。颗粒蛋白家族的蛋白质是DCG组分，尽管其功能尚未完全了解，但数据表明它们除了作为生物活性肽的前体的作用之外，还参与DCG形成和调节蛋白质/肽分泌。基因变异，包括单核苷酸多态性（SNP），与神经精神，内分泌和代谢疾病的关联，涉及特定的分泌蛋白和肽在疾病的发病机制。例如，人脑源性神经营养因子基因196位（G/A）的SNP使蛋白质加工和分泌失调，并导致认知障碍。这更普遍地表明，在编码分泌的生长因子、肽、激素和参与DCG生物发生、蛋白质加工和分泌装置的蛋白质的基因中鉴定的变体可以提供对调节分泌的过程以及当其受损时导致的病症的了解。
The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs), where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs), with neuropsychiatric, endocrine, and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A) of the human brain-derived neurotrophic factor gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired.