MIMM 214 Lecture Notes - Lecture 6: Guanine Nucleotide Exchange Factor, Chronic Granulomatous Disease, Nadph Oxidase

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G-protein-coupled receptors on phagocytes link microbe recognition with increased efficiency of intracellular killing. Gpcrs: receptors belong to the evolutionarily ancient family (g-protein-coupled receptors) seven membrane-spanning segments. Promote inflammation: fmlf receptors: (fmet-leu-phe receptor) Senses the presence of bacteria by recognizing a unique feature of bacterial polypeptides. Steps: in bacteria: protein synthesis initiated with fmet residue (aa only present in. Prokaryotes!: bacterial polypeptides bind activate pathway, fmlf receptor: induces production of reactive oxygen species (ros) in phagolysosome, guidance of neutrophils and monocytes towards site of infection. Ligand activates member of a class of gtp binding proteins. Influences cell motility, metabolism, gene expression, and cell division through activation of several rho family small gtpase proteins. Activation of gtpase: controlled by guanine nucleotide exchange factors (gefs; example: prex1) Rac and rho activation: increase in microbial activity. Ex: nadph oxidase (phagocyte oxidase) unstimulated phagocytes: not activated. Increase of oxygen consumption by cell (respiratory burst, used by neutrophils as early response to infection)

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