Members of our group reported recently that neisseria
infection of human epithelial cells results in accelerated degradation of the major
lysosomal integral membrane protein LAMP1 and that this is due to hydrolysis of this
glycoprotein at its
immunoglobulin A1 (IgA1)-like hinge by the neisseria type 2
IgA1 protease (L. Lin et al., Mol. Microbiol. 24:1083-1094, 1997). We also reported that the
IgA1 protease plays a major role in the ability of the pathogenic neisseriae to survive within epithelial cells and hypothesized that this is due to alteration of lysosomes as a result of
protease-mediated LAMP1 degradation. In this study, we tested the hypothesis that neisseria
infection leads to multiple changes in lysosomes. Here, we report that neisseria
infection also reduces the levels of three other lysosomal markers: LAMP2, lysosomal
acid phosphatase (LAP), and CD63. In contrast, neither the
epidermal growth factor receptor level nor the
beta-tubulin level is affected. A detailed examination of LAMP2 indicated that the reduced LAMP2 levels are not the result of an altered biosynthetic rate or of cleavage by the
IgA1 protease. Nevertheless, the
protease plays a role in reducing LAMP2 and LAP activity levels, as these are partially restored in cells infected with an
iga mutant. We conclude that neisseria
infection results in multiple changes to the lysosomes of infected epithelial cells and that these changes are likely an indirect result of
IgA1 protease-mediated cleavage of LAMP1.