Cell Biology

Prising open the human brain

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Science  29 Nov 2019:
Vol. 366, Issue 6469, pp. 1091-1092
DOI: 10.1126/science.366.6469.1091-d

Meningococcus (Neisseria meningitidis) causes meningitis and rapidly progressing fatal shock, but only in humans. To invade the brain, meningococcus uses its filamentous pili to hijack the β2-adrenergic receptor (β2AR), inducing an allosteric β-arrestin–biased signaling cascade in endothelial cells lining the capillaries of the brain. This cascade allows bacterial colonies to tether to endothelial cells, despite the shear stress of blood flow, and also promotes opening of endothelial junctions, which allows bacteria to penetrate the brain. Virion et al. sought to understand how a G protein–coupled receptor is activated by bacterial type IV pili proteins to transduce a signaling cascade that normally needs a cognate ligand. They found that β2AR activation requires two asparagine-branched glycan chains with terminally exposed sialic acid residues. Meningococcus triggers receptor signaling by exerting mechanical forces on β2AR glycans with its retractable pili. Because human glycans are unusual in exposing sialic acid residues on their glycans, this mechanism may help explain the specificity of meningococcus to its human host.

Nat. Commun. 10, 4752 (2019).

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