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
Biology
Biomedical Research
small interfering RNA
stathmin
TLR3 protein, human
toll like receptor 3
animal
article
astrocyte
brain
gene library
human
immunology
metabolism
microglia
microtubule
mouse
nerve cell
signal transduction
Western blotting
Animals
Astrocytes
Blotting, Western
Brain
Gene Library
Humans
Mice
Microglia
Microtubules
Neurons
RNA, Small Interfering
Signal Transduction
Stathmin
Toll-Like Receptor 3
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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