Formation of Cortical Plaques by Neisseria

Project: Research project

Project Details

Description

DESCRIPTION (provided by the applicant): The Neisseria type IV pilus modulates bacterial infectivity by mediating adhesion and inducing cell signaling pathways. Upon binding its receptor, CD46, the pilus causes a transient increase in cytosolic free Ca2+ levels, triggering endosome and lysosome exocytosis. Piliated bacteria next trigger elongation of microvilli and formation of cortical plaques at the plasma membrane beneath the site of contact. Cortical plaques contain clusters of Opa receptors, transmembrane signaling proteins, actin microfilaments and ezrin, a protein that tethers the membrane to the actin cytoskeleton. These plaques serve multiple signaling functions that promote bacterial infection. Unlike the Ca2+ response, which can be induced with purified pill, cortical plaque formation requires live diplococci and PilT, a protein that functions in pilus assembly and DNA transformation. PilT also controls pilus retraction, a process that drives twitching motility and the ability of diplococci to aggregate into microcolonies. Retraction generates substantial force on the substrate to which the pilus is attached. External forces placed on the membranes of eucaryotic cells result in the induction of kinase cascades, cytoskeleton reorganization and alterations in translation. The tension generated on the plasma membrane by retraction of pili during infection may therefore act as a signal to promote the formation of cortical plaques and subsequent bacterial invasion. Based on these and other observations, we propose a model for early events in pilus-induced cortical plaque formation. In this proposal, we describe experiments to test key predictions of this model.
StatusFinished
Effective start/end date8/1/0111/30/06

Funding

  • National Institutes of Health: $16,793.00
  • National Institutes of Health: $260,170.00
  • National Institutes of Health: $260,170.00
  • National Institutes of Health: $308,836.00
  • National Institutes of Health: $260,170.00
  • National Institutes of Health: $234,153.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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