Ayala B P, Vasquez B, Clary S, Tainer J A, Rodland K, So M
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Cell Microbiol. 2001 Apr;3(4):265-75. doi: 10.1046/j.1462-5822.2001.00112.x.
The IgA1 protease secreted by the pathogenic Neisseriae cleaves Lamp1, a major integral membrane glycoprotein of lysosomes, and significantly reduces its steady-state levels in an infected cell. IgA1 protease hydrolysis of Lamp1 is inefficient at the low pH of lysosomes, strongly suggesting that the enzyme is unlikely to reduce Lamp1 levels within lysosomes to any appreciable extent. We therefore explored the possibility that the protease may reach Lamp1 through an alternative route. We demonstrate that Neisseria pili induce a transient increase in the levels of cytosolic free Ca2+ in A431 human epithelial cells, as demonstrated previously for ME180 cells. This Ca2+ flux triggers lysosome exocytosis, quickly altering the cellular distribution of Lamp1 and increasing surface Lamp1 levels. Finally, we demonstrate that surface Lamp1 is cleaved by IgA1 protease secreted by adherent bacteria. We conclude that the pilus-induced Ca2+ flux increases the amount of Lamp1 that is cleavable by the IgA1 protease.
致病性奈瑟菌分泌的IgA1蛋白酶可切割溶酶体的主要整合膜糖蛋白Lamp1，并显著降低其在感染细胞中的稳态水平。IgA1蛋白酶对Lamp1的水解在溶酶体的低pH值下效率低下，这强烈表明该酶不太可能在溶酶体内将Lamp1水平降低到任何可观的程度。因此，我们探讨了蛋白酶可能通过另一条途径作用于Lamp1的可能性。我们证明，奈瑟菌菌毛可诱导A431人上皮细胞中胞质游离Ca2+水平短暂升高，正如先前在ME180细胞中所证明的那样。这种Ca2+通量触发溶酶体胞吐作用，迅速改变Lamp1的细胞分布并增加表面Lamp1水平。最后，我们证明表面Lamp1可被黏附细菌分泌的IgA1蛋白酶切割。我们得出结论，菌毛诱导的Ca2+通量增加了可被IgA1蛋白酶切割的Lamp1的量。
