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Related Concept Videos

Complement System01:27

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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Related Experiment Video

Updated: Jun 22, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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Complement Membrane Attack Complexes Disrupt Proteostasis to Function as Intracellular Alarmins.

Dan Jane-Wit1, Guiyu Song2, Liying He1

  • 1Yale University.

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PubMed
Summary
This summary is machine-generated.

Membrane attack complexes (MACs) internalize, forming aggregates that trigger inflammation. This process involves C9 protein, aggrephagy, and ZFYVE21, revealing MACs as intracellular alarmins.

Keywords:
RNF34Rab5ZFYVE21aggrephagyalarmincomplementendosomeendothelial cellmacroautophagymembrane attack complex

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Membrane attack complexes (MACs) are known to cause cell lysis.
  • Internalized MACs are implicated in NF-kB activation and tissue inflammation.

Purpose of the Study:

  • To investigate the role of C9, a MAC-associated protein, in proteostasis and immune signaling.
  • To elucidate the mechanism by which C9 aggregates induce inflammatory responses.

Main Methods:

  • Utilized cell culture models and mouse models.
  • Investigated protein aggregation, endocytosis, and aggrephagy pathways.
  • Employed gene-deficient mice to study the role of ZFYVE21.

Main Results:

  • Surface-bound C9 is internalized, aggregated within endosomes, and promotes loss of proteostasis.
  • C9 aggregates stimulate NF-kB, inflammatory genes, and endothelial cell activation via aggrephagy.
  • ZFYVE21 is crucial for C9 aggrephagy and stabilization of RNF34, impacting tissue injury.

Conclusions:

  • C9 aggregates act as intracellular alarmins, linking MACs to inflammation beyond cytotoxicity.
  • The C9-mediated aggrephagy pathway involving ZFYVE21 is a novel mechanism of immune activation.
  • Targeting this pathway may offer therapeutic strategies for inflammatory diseases.