Breaking the Barrier

Science Signaling  07 Jul 2009:
Vol. 2, Issue 78, pp. ec229
DOI: 10.1126/scisignal.278ec229

Being able to deliver drugs into the brain to treat degenerative diseases such as Alzheimer or Parkinson diseases requires the ability to traverse the blood brain barrier (BBB). Understanding the formation of the very specific adherent junctions (AJ) and tight junctions present at the BBB cell junctions is a prerequisite to the design of such therapeutics. However, diminishing the expression of any one component involved in the formation of these intercellular junctions destroys them. Coureuil et al. exploited the specific recruitment of AJ proteins by Neisseria meningitidis to dissect this process. Adhesion of the bacteria to human brain endothelial cells recruited the polarity complex Par3-Par6-PKCζ (partitioning defective 3–partitioning defective 6–protein kinase Cζ) required for the establishment of eukaryotic cell polarity and the formation of intercellular junctions. The bacterial recruitment of the polarity complex depleted junctional proteins at the cell-cell interface opening the intercellular junctions at the brain-endothelial interface.

M. Coureuil, G. Mikaty, F. Miller, H. Lécuyer, C. Bernard, S. Bourdoulous, G. Duménil, R.-M. Mège, B. B. Weksler, I. A. Romero, P.-O. Couraud, X. Nassif, Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science 325, 83–87 (2009).[Abstract] [Full Text]