Cellular and Molecular Life Sciences

, Volume 74, Issue 7, pp 1211–1229 | Cite as

Assembly and regulation of ASC specks

  • Florian Hoss
  • Juan F. Rodriguez-Alcazar
  • Eicke LatzEmail author


The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease.


Speck PYD CARD Fibril Prionoid PTM COP POP 



Amino acid


Absent in melanoma 2


Apoptotic protease-activating factor 1


Apoptosis-associated speck-like protein containing a CARD


Cryopyrin-associated periodic syndrome


Caspase-recruitment domain


CARD-only protein


Damage-associated molecular pattern


Death domain


Death effector domain


Ubiquitin-activating enzyme


Ubiquitin-conjugating enzyme


Ubiquitin-ligation enzyme


Electrostatic potential surface patch


Familial cold autoinflammatory syndrome


Familial Mediterranean fever


Hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats


Heme-oxidized IRP2 ubiquitin ligase-1


HOIL-1 interacting protein


IκB kinase




c-Jun N-terminal kinase




Linear ubiquitin chain assembly complex


Mitochondrial antiviral-signaling


Mediterranean fever


Myxoma virus


NLR family apoptosis inhibitory protein


Nuclear factor kappa-light-chain enhancer of activated B-cells


Nucleotide-binding oligomerization domain (NOD)-like receptor


NOD-, LRR-, CARD-containing


NOD-, leucine-rich repeat (LRR)-, PYD-containing


Nucleotide oligomerization domain


Neonatal-onset multisystem inflammatory disorder


Pathogen-associated molecular pattern


Pyrin-only protein


Pattern-recognition receptor


Post-translational modification


PYD and CARD domain containing


Pyrin domain


Pyrin domain containing


Receptor-interacting serine/threonine-protein kinase 2


SHANK-associated RH domain interactor


Swine pox virus


Stimulated emission depletion


Spleen tyrosine kinase


Target of methylation-induced gene silencing 1


Tumor necrosis factor


TNF receptor-associated factor 3


Virus-encoded POP


Vesicular stomatitis virus



The ASC speck STED image showed in Fig. 2 was recorded with the help of Bjørnar Sporsheim at the Cellular and Molecular Imaging Core Facility (CMIC), Norwegian University of Science and Technology (NTNU). We thank Andrea Stutz for critical reading of the manuscript.


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.Institute of Innate ImmunityUniversity Hospitals, University of BonnBonnGermany
  2. 2.Department of Infectious Diseases and ImmunologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.German Center for Neurodegenerative DiseasesBonnGermany
  4. 4.Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation ResearchNorwegian University of Science and TechnologyTrondheimNorway

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