Jena Bhanu P
Wayne State University School of Medicine, Department of Physiology, Detroit, MI, USA.
Discoveries (Craiova). 2014 Jul-Sep;2(3). doi: 10.15190/d.2014.16.
Macromolecular structures embedded in the cell plasma membrane called 'porosomes', are involved in the regulated fractional release of intravesicular contents from cells during secretion. Porosomes range in size from 15 nm in neurons and astrocytes to 100-180 nm in the exocrine pancreas and neuroendocrine cells. Porosomes have been isolated from a number of cells, and their morphology, composition, and functional reconstitution well documented. The 3D contour map of the assembly of proteins within the porosome complex, and its native X-ray solution structure at sub-nm resolution has also advanced. This understanding now provides a platform to address diseases that may result from secretory defects. Water and ion binding to mucin impart hydration, critical for regulating viscosity of the mucus in the airways epithelia. Appropriate viscosity is required for the movement of mucus by the underlying cilia. Hence secretion of more viscous mucus prevents its proper transport, resulting in chronic and fatal airways disease such as cystic fibrosis (CF). CF is caused by the malfunction of CF transmembrane conductance regulator (CFTR), a chloride channel transporter, resulting in viscous mucus in the airways. Studies in mice lacking functional CFTR secrete highly viscous mucous that adhered to the epithelium. Since CFTR is known to interact with the t-SNARE protein syntaxin-1A, and with the chloride channel CLC-3, which are also components of the porosome complex, the interactions between CFTR and the porosome complex in the mucin-secreting human airway epithelial cell line Calu-3 was hypothesized and tested. Results from the study demonstrate the presence of approximately 100 nm in size porosome complex composed of 34 proteins at the cell plasma membrane in Calu-3 cells, and the association of CFTR with the complex. In comparison, the nuclear pore complex measures 120 nm and is comprised of over 500 protein molecules. The involvement of CFTR in porosome-mediated mucin secretion is hypothesized, and is currently being tested.
嵌入细胞质膜中的称为“孔体”的大分子结构，参与细胞在分泌过程中从细胞内泡内容物的调节性部分释放。孔体的大小范围从神经元和星形胶质细胞中的15纳米到外分泌胰腺和神经内分泌细胞中的100 - 180纳米。孔体已从多种细胞中分离出来，其形态、组成和功能重建都有详细记录。孔体复合物内蛋白质组装的三维轮廓图及其亚纳米分辨率的天然X射线溶液结构也有进展。这种认识现在为解决可能由分泌缺陷导致的疾病提供了一个平台。水和离子与粘蛋白结合赋予水合作用，这对于调节气道上皮中粘液的粘度至关重要。适当的粘度是粘液在下面的纤毛作用下移动所必需的。因此，分泌更粘稠的粘液会阻止其正常运输，导致慢性和致命的气道疾病，如囊性纤维化（CF）。CF是由CF跨膜电导调节因子（CFTR），一种氯离子通道转运蛋白功能失常引起的，导致气道中出现粘稠的粘液。对缺乏功能性CFTR的小鼠的研究表明，它们分泌的高度粘稠粘液会附着在上皮细胞上。由于已知CFTR与t - SNARE蛋白 syntaxin - 1A以及氯离子通道CLC - 3相互作用，而它们也是孔体复合物的组成部分，因此推测并测试了CFTR与分泌粘蛋白的人气道上皮细胞系Calu - 3中孔体复合物之间的相互作用。研究结果表明，在Calu - 3细胞的细胞质膜上存在由34种蛋白质组成的大小约为100纳米的孔体复合物，并且CFTR与该复合物相关联。相比之下核孔复合物尺寸为120纳米且由超过500个蛋白质分子组成。推测CFTR参与孔体介导的粘蛋白分泌，目前正在进行测试。
