The IL1α-S100A13 Heterotetrameric Complex Structure

Mohan, Sumathy; Yu, Chin

doi:10.1074/jbc.m110.201954

Cited by 29 publications

(30 citation statements)

References 57 publications

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“…S100A13 belongs to the S100 protein family, which is a part of the Ca 2+ -binding protein superfamily with an EF hand domain. S100A13 is an intracellular protein, which plays a crucial role in the non-classical pathway for extracellular release of FGF-1 and IL-1α, both of which lack signal peptides, by forming heterotetrameric complexes [ 25 – 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…S100A13 is a Ca 2+ -binding protein that belongs to the S100 protein family. S100A13 crucially forms heterotetrameric complexes via non-classical pathways for the secretion of FGF-1 and IL-1α, both of which lack a signal peptide for classical secretion[ 25 – 27 ]. S100A13 has been implicated in angiogenesis[ 35 – 37 ], tumor development[ 38 ], and chronic inflammation[ 39 ].…”

Section: Discussionmentioning

confidence: 99%

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Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis

et al. 2015

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The platelet receptor CLEC-2 is involved in thrombosis/hemostasis, but its ligand, podoplanin, is expressed only in advanced atherosclerotic lesions. We investigated CLEC-2 ligands in vessel walls. Recombinant CLEC-2 bound to early atherosclerotic lesions and normal arterial walls, co-localizing with vascular smooth muscle cells (VSMCs). Flow cytometry and immunocytochemistry showed that recombinant CLEC-2, but not an anti-podoplanin antibody, bound to VSMCs, suggesting that CLEC-2 ligands other than podoplanin are present in VSMCs. VSMCs stimulated platelet granule release and supported thrombus formation under flow, dependent on CLEC-2. The time to occlusion in a FeCl3-induced animal thrombosis model was significantly prolonged in the absence of CLEC-2. Because the internal elastic lamina was lacerated in our FeCl3-induced model, we assume that the interaction between CLEC-2 and its ligands in VSMCs induces thrombus formation. Protein arrays and Biacore analysis were used to identify S100A13 as a CLEC-2 ligand in VSMCs. However, S100A13 is not responsible for the above-described VSMC-induced platelet activation, because S100A13 is not expressed on the surface of normal VSMCs. S100A13 was released upon oxidative stress and expressed in the luminal area of atherosclerotic lesions. Suspended S100A13 did not activate platelets, but immobilized S100A13 significantly increased thrombus formation on collagen-coated surfaces. Taken together, we proposed that VSMCs stimulate platelets through CLEC-2, possibly leading to thrombus formation after plaque erosion and stent implantation, where VSMCs are exposed to blood flow. Furthermore, we identified S100A13 as one of the ligands on VSMCs.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis

et al. 2015

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“…137 Interestingly, increased levels of Cu 2+ were also shown to promote IL-1α secretion through an S100A13-dependent secretion mechanism. 139, 140 Further differentiating itself from IL-1β and HMGB1, IL-1α activation and secretion is inhibited by autophagy. Indeed, in the context of Mycobacterium tuberculosis infection, ATG5-dependent autophagy was shown to block both the calpain-dependent activation of IL-1α and its secretion, thereby limiting lung inflammation and tissue damage.…”

Section: Interleukin-1αmentioning

confidence: 99%

HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins

2016

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Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline-encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells. However, a group of proteins referred to as alarmins have both intracellular and extracellular functions which have been the subject of intense research. Indeed, alarmins can either exert beneficial cell housekeeping functions, leading to tissue repair, or provoke deleterious uncontrolled inflammation. This group of proteins includes the high-mobility group box 1 protein (HMGB1), interleukin (IL)-1α, IL-33 and the Ca2+-binding S100 proteins. These dual-function proteins share conserved regulatory mechanisms, such as secretory routes, post-translational modifications and enzymatic processing, that govern their extracellular functions in time and space. Release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development.

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“…Amongst the S100 proteins, the role of S100A13 in the non-classical secretory pathway is the best described, forming well characterised stress-dependent multimeric complexes with specific cytokines such as interleukin 1a and fibroblast growth factor 1 (FGF) (for example see [15]). However, the exact mechanisms in place to facilitate the release of S100 proteins generally remain unclear, but seem to require proper microtubule and actin cytoskeletal organisation, at least for some of the factors [16,17].…”

Section: Introductionmentioning

confidence: 99%

Joining S100 proteins and migration: for better or for worse, in sickness and in health

Gross

Sin

Barraclough

et al. 2013

Cell. Mol. Life Sci.

155

148

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The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used.

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The IL1α-S100A13 Heterotetrameric Complex Structure

Cited by 29 publications

References 57 publications

Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis

Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis

HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins

Joining S100 proteins and migration: for better or for worse, in sickness and in health

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