Print Email Facebook Twitter The microtubule regulator stathmin is an endogenous protein agonist for TLR3. Title The microtubule regulator stathmin is an endogenous protein agonist for TLR3. Author Bsibsi, M. Bajramovic, J.J. Vogt, M.H. van Duijvenvoorden, E. Baghat, A. Persoon-Deen, C. Tielen, F. Verbeek, R. Huitinga, I. Ryffel, B. Kros, A. Gerritsen, W.H. Amor, S. van Noort, J.M. TNO Kwaliteit van Leven Publication year 2010 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. Chemicals/CAS: stathmin, 126880-56-6; RNA, Small Interfering; Stathmin; TLR3 protein, human; Toll-Like Receptor 3 Subject BiologyBiomedical Researchsmall interfering RNAstathminTLR3 protein, humantoll like receptor 3animalarticleastrocytebraingene libraryhumanimmunologymetabolismmicrogliamicrotubulemousenerve cellsignal transductionWestern blottingAnimalsAstrocytesBlotting, WesternBrainGene LibraryHumansMiceMicrogliaMicrotubulesNeuronsRNA, Small InterferingSignal TransductionStathminToll-Like Receptor 3 To reference this document use: http://resolver.tudelft.nl/uuid:031a82b3-48c1-440b-be74-0fbc98d2c247 TNO identifier 364423 ISSN 1550-6606 Source Journal of immunology, 184 (12), 6929-6937 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.