Program in Molecular Medicine
Cell Biology | Cells | Hemic and Immune Systems | Molecular Biology | Pathological Conditions, Signs and Symptoms | Translational Medical Research
The centrosome is critical for cell division, ciliogenesis, membrane trafficking, and immunological synapse function. The immunological synapse is part of the immune response, which is often accompanied by fever/heat stress (HS). Here we provide evidence that HS causes deconstruction of all centrosome substructures primarily through degradation by centrosome-associated proteasomes. This renders the centrosome nonfunctional. Heat-activated degradation is centrosome selective, as other nonmembranous organelles (midbody, kinetochore) and membrane-bounded organelles (mitochondria) remain largely intact. Heat-induced centrosome inactivation was rescued by targeting Hsp70 to the centrosome. In contrast, Hsp70 excluded from the centrosome via targeting to membranes failed to rescue, as did chaperone inactivation. This indicates that there is a balance between degradation and chaperone rescue at the centrosome after HS. This novel mechanism of centrosome regulation during fever contributes to immunological synapse formation. Heat-induced centrosome inactivation is a physiologically relevant event, as centrosomes in leukocytes of febrile patients are disrupted. Cell Biology under license from the author(s).
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© 2015 Vertii et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
DOI of Published Version
Mol Biol Cell. 2015 Oct 1;26(19):3451-63. doi: 10.1091/mbc.E15-03-0158. Epub 2015 Aug 12. Link to article on publisher's site
Molecular biology of the cell
Vertii, Anastassiia; Zimmerman, Wendy; Ivshina, Mariya; and Doxsey, Stephen J., "Centrosome-intrinsic mechanisms modulate centrosome integrity during fever" (2015). UMass Center for Clinical and Translational Science Supported Publications. 182.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.