Chromogranin A fragments modulate cell adhesion - Identification and characterization of a pro-adhesive domain
Chromogranin A fragments modulate cell adhesion - Identification and characterization of a pro-adhesive domain
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DOI：
10.1074/jbc.272.33.20835
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发表时间：
1997-08-15
影响因子：
4.8
通讯作者：
Corti, A
中科院分区：
文献类型：
--
作者：
Gasparri, A;Sidoli, A;Corti, A
嗜铬粒蛋白A是一种由许多神经内分泌细胞分泌的糖蛋白，虽然已经提出了它的几种功能，但这种蛋白及其蛋白水解片段的生理作用尚未确定。我们发现嗜铬粒蛋白A片段的混合物可以抑制成纤维细胞的粘附。通过有限的胰蛋白酶处理，抗粘附活性转化为促粘附活性。与残基1-78和1-115对应的重组n端片段以及包含残基7-57的合成肽也观察到预粘附作用。这些片段诱导成纤维细胞在涂有ⅰ型或ⅳ型胶原蛋白、层粘连蛋白、胎牛血清（FCS）的板上粘附和扩散，但在牛血清白蛋白上没有。粘附试验所需的长孵育时间（4小时）和最佳粘附所需的FCS表明，粘附活性可能是间接的，需要FCS中存在或由细胞产生的其他蛋白质。这些发现提示嗜铬粒蛋白A及其片段可能在细胞粘附调控中起作用。由于嗜铬粒蛋白A被集中储存在颗粒内，并在适当刺激后由神经内分泌细胞和神经元迅速释放，因此该蛋白可能对受刺激细胞局部控制细胞粘附具有重要意义。
Although several functions have been suggested for chromogranin A, a glycoprotein secreted by many neuroendocrine cells, the physiological role of this protein and of its proteolytic fragments has not been established. We have found that mixtures of chromogranin A fragments can inhibit fibroblast adhesion. The anti-adhesive activity was converted into pro-adhesive activity by limited trypsin treatment. Pro-adhesive effects were observed also with recombinant N-terminal fragments corresponding to residues 1-78 and 1-115 and with a synthetic peptide encompassing the residues 7-57. These fragments induced adhesion and spreading of fibroblasts on plates coated with collagen I or IV, laminin, fetal calf serum (FCS) but not on bovine serum albumin. The long incubation time required for adhesion assays (4 h) and the FCS requirements for optimal adhesion suggest that the adhesive activity is likely indirect and requires other proteins present in the FCS or made by the cells.These findings suggest that chromogranin A and its fragments could play a role in the regulation of cell adhesion. Since chromogranin A is concentrated and stored within granules and rapidly released by neuroendocrine cells and neurons after an appropriate stimulus, this protein could be important for the local control of cell adhesion by stimulated cells.