Movitz C, Sjölin C, Dahlgren C
The Phagocyte Research Laboratory, Department of Medical Microbiology and Immunology, Göteborg University, Guldhedsgatan 10, S-413 46, Göteborg, Sweden.
Biochim Biophys Acta. 1999 Jan 12;1416(1-2):101-8. doi: 10.1016/s0005-2736(98)00212-0.
A truncated form of annexin I, formed during Ca2+-induced translocation to neutrophil specific granules and secretory vesicles/plasma membranes, is generated through the action of an endogenous membrane protease. The cleavage of annexin I is inhibited by the metalloprotease inhibitor 1,10-phenanthroline as well as by Triton X-100 and dithiothreitol, classifying the protease as a membrane-bound, thiol-dependent metalloprotease. The cleavage site is located close to the N-terminal of annexin I, leaving a truncated form of the molecule, des1-8 annexin I, that contains the Ca2+-binding sites, as well as a number of phosphorylation sites of importance for the function of the protein. When assessing binding capacity to different neutrophil organelles, full-length annexin I bound to azurophil granules, specific granules, and secretory vesicles/plasma membranes, while des1-8 annexin I only bound to specific granules and secretory vesicles/plasma membranes, but not to azurophil granules (C. Sjölin, C. Dahlgren, Biochim. Biophys. Acta 1281 (1996) 227-234). This implies that there are different mechanisms of binding to neutrophil organelles of full-length annexin I and the truncated form, and that cleavage of annexin I might be of regulatory importance for the degranulation process.
膜联蛋白I的一种截短形式是在钙离子诱导其向中性粒细胞特异性颗粒和分泌囊泡/质膜转位的过程中形成的，它是由一种内源性膜蛋白酶作用产生的。膜联蛋白I的切割受到金属蛋白酶抑制剂1,10 - 菲咯啉以及 Triton X - 100和二硫苏糖醇的抑制，这将该蛋白酶归类为一种膜结合的、硫醇依赖性金属蛋白酶。切割位点靠近膜联蛋白I的N端，产生一种截短形式的分子，即des1 - 8膜联蛋白I，它含有钙离子结合位点以及一些对该蛋白质功能很重要的磷酸化位点。在评估与不同中性粒细胞细胞器的结合能力时，全长膜联蛋白I与嗜天青颗粒、特异性颗粒以及分泌囊泡/质膜结合，而des1 - 8膜联蛋白I仅与特异性颗粒和分泌囊泡/质膜结合，不与嗜天青颗粒结合（C. 舍林，C. 达尔格伦，《生物化学与生物物理学报》1281 (1996) 227 - 234）。这意味着全长膜联蛋白I和截短形式与中性粒细胞细胞器的结合机制不同，并且膜联蛋白I的切割可能对脱颗粒过程具有调节重要性。
