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Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Related Experiment Video

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A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
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TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation.

Lorenza Magno1, Tom D Bunney2, Emma Mead3

  • 1Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK. l.magno@ucl.ac.uk.

Molecular Neurodegeneration
|April 7, 2021
PubMed
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Microglia, the brain's immune cells, are central to neurodegeneration. Recent studies reveal how TREM2 and PLCγ2 gene functions in microglia offer new therapeutic avenues for these disorders.

Keywords:
Alzheimer’s diseaseImmune systemMicrogliaProtein networksSignallingTherapeutic intervention

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Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Genome-wide association studies (GWAS) highlight the critical role of microglia in neurodegenerative diseases.
  • A gap exists in understanding the specific gene-to-function mechanisms underlying microglial involvement.
  • Microglia are the resident innate immune cells of the central nervous system.

Purpose of the Study:

  • To review recent advances in understanding microglial function in neurodegeneration.
  • To discuss the roles of TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) and PLCγ2 (Phospholipase C gamma2) in neurodegenerative disorders.
  • To explore potential therapeutic strategies targeting microglial pathways.

Main Methods:

  • Review of recent scientific literature and key research reports.
  • Analysis of genetic studies implicating microglial genes in neurodegeneration.
  • Discussion of functional studies on TREM2 and PLCγ2 in microglial cells.

Main Results:

  • Recent reports provide mechanistic insights into TREM2 and PLCγ2 functions in microglia.
  • These gene products are crucial for microglial activity in the context of neurodegeneration.
  • Advances illuminate the pathway from gene discovery to cellular function.

Conclusions:

  • Understanding TREM2 and PLCγ2 function in microglia is key to unraveling neurodegeneration.
  • These findings open new opportunities for developing targeted therapies.
  • Further research into microglial biology holds promise for treating neurological disorders.