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We previously identified PLEKHA7 and other junctional proteins as host factors mediating death by S. aureus α-toxin, but the mechanism through which junctions promote toxicity was unclear. Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. ADAM10 is locked at junctions through binding of its cytoplasmic C terminus to afadin. Junctionally clustered ADAM10 supports the efficient formation of stable toxin pores. Instead, disruption of the PLEKHA7-PDZD11 complex inhibits ADAM10 and toxin junctional clustering. This promotes toxin pore removal from the cell surface through an actin- and macropinocytosis-dependent process, resulting in cell recovery from initial injury and survival. These results uncover a dock-and-lock molecular mechanism to target ADAM10 to junctions and provide a paradigm for how junctions regulate transmembrane receptors through their clustering.
Pubmed ID: 30463011 RIS Download
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View all literature mentionsMolecular biology software for visualizing and documenting gene constructs for InFusion cloning, Gibson assembly, restriction cloning, PCR, and mutagenesis.
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View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsThis polyclonal targets Adam10
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets Staphylococcal alpha-Toxin antibody produced in rabbit
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis polyclonal targets His-probe (H-15)
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets HA Tag
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets Staphylococcal alpha-Toxin antibody produced in rabbit
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets HA Tag
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets His-probe (H-15)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
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