TY - JOUR
T1 - Pyrin and ASC Co-localize to cellular sites that are rich in polymerizing actin
AU - Waite, Andrea L.
AU - Schaner, Philip
AU - Hu, Chunbo
AU - Richards, Neil
AU - Balci-Peynircioglu, Banu
AU - Hong, Arthur
AU - Fox, Michelle
AU - Gumucio, Deborah L.
N1 - Funding Information:
This work was supported by (NIH R01-AI053262). P.S. was supported by the Organogenesis Training Program (NIH/NICHD T32-HL07505).
PY - 2009/1
Y1 - 2009/1
N2 - Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV locus, which encodes the protein pyrin. While it is known that pyrin is expressed in myeloid cells and several fibroblastic cell types, the exact function of pyrin in these cells and the mechanism underlying the pathological effect of pyrin mutations have yet to be revealed. Here, we document that in migrating human monocytes, pyrin protein is dramatically polarized at the leading edge, where it co-localizes with polymerizing actin. ASC (Apoptosis-associated Speck protein with CARD domain), a known pyrininteracting protein and a critical component of the inflammasome, is also located at the leading edge in migrating monocytes. Similarly, both pyrin and ASC concentrate in dynamically polymerizing actin-rich tails generated by Listeria monocytogenes. Pyrin's B-box and coiled-coil region is required for its association with Listeria tails. Pyrin also binds, with low affinity and via the same domains, to actin, VASP, and Arp3. Though disease-causing mutations in pyrin do not appear to alter its localization to the leading edge or to Listeria rocket tails, they could potentially have important functional consequences in the context of processes such as migration and cell synapse formation. The co-localization of pyrin and ASC together at such sites may provide an important link between cytoskeletal signaling and inflammasome function.
AB - Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV locus, which encodes the protein pyrin. While it is known that pyrin is expressed in myeloid cells and several fibroblastic cell types, the exact function of pyrin in these cells and the mechanism underlying the pathological effect of pyrin mutations have yet to be revealed. Here, we document that in migrating human monocytes, pyrin protein is dramatically polarized at the leading edge, where it co-localizes with polymerizing actin. ASC (Apoptosis-associated Speck protein with CARD domain), a known pyrininteracting protein and a critical component of the inflammasome, is also located at the leading edge in migrating monocytes. Similarly, both pyrin and ASC concentrate in dynamically polymerizing actin-rich tails generated by Listeria monocytogenes. Pyrin's B-box and coiled-coil region is required for its association with Listeria tails. Pyrin also binds, with low affinity and via the same domains, to actin, VASP, and Arp3. Though disease-causing mutations in pyrin do not appear to alter its localization to the leading edge or to Listeria rocket tails, they could potentially have important functional consequences in the context of processes such as migration and cell synapse formation. The co-localization of pyrin and ASC together at such sites may provide an important link between cytoskeletal signaling and inflammasome function.
KW - ASC
KW - Actin
KW - Familial mediterranean fever
KW - Pyrin
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U2 - 10.3181/0806-RM-184
DO - 10.3181/0806-RM-184
M3 - Article
C2 - 19109554
AN - SCOPUS:60549111042
SN - 1535-3702
VL - 234
SP - 40
EP - 52
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 1
ER -