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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 Latz
Review

Abstract

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.

Keywords

Speck PYD CARD Fibril Prionoid PTM COP POP 

Abbreviations

aa

Amino acid

AIM2

Absent in melanoma 2

APAF-1

Apoptotic protease-activating factor 1

ASC

Apoptosis-associated speck-like protein containing a CARD

CAPS

Cryopyrin-associated periodic syndrome

CARD

Caspase-recruitment domain

COP

CARD-only protein

DAMP

Damage-associated molecular pattern

DD

Death domain

DED

Death effector domain

E1

Ubiquitin-activating enzyme

E2

Ubiquitin-conjugating enzyme

E3

Ubiquitin-ligation enzyme

EPSP

Electrostatic potential surface patch

FCAS

Familial cold autoinflammatory syndrome

FMF

Familial Mediterranean fever

HIN200

Hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats

HOIL-1

Heme-oxidized IRP2 ubiquitin ligase-1

HOIP

HOIL-1 interacting protein

IKK

IκB kinase

IL

Interleukin

Jnk

c-Jun N-terminal kinase

LPS

Lipopolysaccharide

LUBAC

Linear ubiquitin chain assembly complex

MAVS

Mitochondrial antiviral-signaling

MEFV

Mediterranean fever

MV

Myxoma virus

NAIP

NLR family apoptosis inhibitory protein

NF-κB

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

NLR

Nucleotide-binding oligomerization domain (NOD)-like receptor

NLRC

NOD-, LRR-, CARD-containing

NLRP

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

NOD

Nucleotide oligomerization domain

NOMID

Neonatal-onset multisystem inflammatory disorder

PAMP

Pathogen-associated molecular pattern

POP

Pyrin-only protein

PRR

Pattern-recognition receptor

PTM

Post-translational modification

PYCARD

PYD and CARD domain containing

PYD

Pyrin domain

Pydc

Pyrin domain containing

RIPK2

Receptor-interacting serine/threonine-protein kinase 2

SHARPIN

SHANK-associated RH domain interactor

SPV

Swine pox virus

STED

Stimulated emission depletion

Syk

Spleen tyrosine kinase

TMS1

Target of methylation-induced gene silencing 1

TNF

Tumor necrosis factor

TRAF3

TNF receptor-associated factor 3

vPOP

Virus-encoded POP

VSV

Vesicular stomatitis virus

Notes

Acknowledgments

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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