Pyrin Modulates the Intracellular Distribution of PSTPIP1

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Pyrin Modulates the Intracellular Distribution of PSTPIP1

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Title: Pyrin Modulates the Intracellular Distribution of PSTPIP1
Author: Waite, Andrea L.; Schaner, Philip; Richards, Neil; Balci-Peynircioglu, Banu; Masters, Seth L.; Brydges, Susannah D.; Hong, Arthur; Yilmaz, Engin; Kastner, Daniel L.; Gumucio, Deborah L.; May, Robin Charles; Fox, Michelle; Reinherz, Ellis Leonard

Note: Order does not necessarily reflect citation order of authors.

Citation: Waite, Andrea L., Philip Schaner, Neil Richards, Banu Balci-Peynircioglu, Seth L. Masters, Susannah D. Brydges, Michelle Fox, et al. 2009. Pyrin Modulates the Intracellular Distribution of PSTPIP1. PLoS ONE 4(7) e6147.
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Abstract: PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. Mutations in PSTPIP1 cause PAPA syndrome (Pyogenic sterile Arthritis, Pyoderma gangrenosum, and Acne), an autoinflammatory disease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial Mediterranean fever (FMF), a related autoinflammatory disorder. Since disease-associated mutations in PSTPIP1 enhance pyrin binding, PAPA syndrome and FMF are thought to share a common pathoetiology. The studies outlined here describe several new aspects of PSTPIP1 and pyrin biology. We document that PSTPIP1, which has homology to membrane-deforming BAR proteins, forms homodimers and generates membrane-associated filaments in native and transfected cells. An extended FCH (Fes-Cip4 homology) domain in PSTPIP1 is necessary and sufficient for its self-aggregation. We further show that the PSTPIP1 filament network is dependent upon an intact tubulin cytoskeleton and that the distribution of this network can be modulated by pyrin, indicating that this is a dynamic structure. Finally, we demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC, another pyrin binding protein. ASC specks are associated with inflammasome activity. PSTPIP1 molecules with PAPA-associated mutations are recruited by pyrin to ASC specks with particularly high efficiency, suggesting a unique mechanism underlying the robust inflammatory phenotype of PAPA syndrome.
Published Version: doi:10.1371/journal.pone.0006147
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702820/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4633207

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