The microtubule regulator stathmin is an endogenous protein agonist for TLR3.
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| Abstract |
TLR3 recognizes dsRNAs and is considered of key importance to antiviral host-defense responses. TLR3 also triggers neuroprotective responses in astrocytes and controls the growth of axons and neuronal progenitor cells, suggesting additional roles for TLR3-mediated signaling in the CNS. This prompted us to search for alternative, CNS-borne protein agonists for TLR3. A genome-scale functional screening of a transcript library from brain tumors revealed that the microtubule regulator stathmin is an activator of TLR3-dependent signaling in astrocytes, inducing the same set of neuroprotective factors as the known TLR3 agonist polyinosinic:polycytidylic acid. This activity of stathmin crucially depends on a long, negatively charged alpha helix in the protein. Colocalization of stathmin with TLR3 on astrocytes, microglia, and neurons in multiple sclerosis-affected human brain indicates that as an endogenous TLR3 agonist, stathmin may fulfill previously unsuspected regulatory roles during inflammation and repair in the adult CNS.
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| Authors | Malika Bsibsi, Jeffrey J Bajramovic, Mario H J Vogt, Eveline van Duijvenvoorden, Aabed Baghat, Carla Persoon-Deen, Frans Tielen, Richard Verbeek, Inge Huitinga, Bernhard Ryffel, Alexander Kros, Wouter H Gerritsen, Sandra Amor, Johannes M van Noort |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 12 Pg. 6929-37 (Jun 15 2010) ISSN: 1550-6606 [Electronic] United States |
| PMID | 20483774 (Publication Type: Journal Article) |
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