The pilus-induced Ca2+ flux triggers lysosome exocytosis and increases the amount of Lamp1 accessible to Neisseria IgA1 protease.
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.
Ayala
B P
BP
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA. ayalap@OHSU.EDU
Vasquez
B
B
Clary
S
S
Tainer
J A
JA
Rodland
K
K
So
M
M
D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004848:Epithelium / Q000382:microbiology; D005089:Exocytosis / Q000502:physiology; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009343:Neisseria / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D012697:Serine Endopeptidases / Q000378:metabolism*
D015703:Antigens, CD; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase; D002118:Calcium