Cell Communication PDF

CELL COMMUNICATION  Inner hair cell 2 hair cell Outer Lu et al., 2016  3 Extracellular signal molecules Unicellular organisms Response to extracellular signal mol...

CELL COMMUNICATION  Inner hair cell 2 hair cell Outer Lu et al., 2016  3 Extracellular signal molecules Unicellular organisms Response to extracellular signal molecules altered cell behavior Multicellular organism Response to signal molecules: Altered metabolism Altered tissue growth and differentiation Protein synthesis and secretion Altered intracellular and extracellular composition Signal molecules : ligand bind to specific receptor - on/in target cell cell-surface receptors act as signal transducers by converting an extracellular ligand-binding event into intracellular signals that alter the behavior of the target cell  4 Signal molecules ≤10-8M  activate cell signalling & alter cell behavior Receptor : Intracellular  hidrophobic/small signal molecules Extracellular  hidrophilic signal molecules  Signaling in multicellular organisms Homocrine Autocrine Neural Endocrine Exocrine Paracrine Direct Communication Indirect communication  7 Speed of a response to an extracellular signal depends on: The mechanism of signal delivery the nature of the target cell’s response. Response : rapid response: changes in proteins already present in the cell: an allosteric change in a neurotransmitter-gated ion channel protein phosphorylation Slow response changes in gene expression and the synthesis of new proteins  8 Different Types of Cells Usually Respond Differently to the Same Extracellular Signal Molecule A cell’s response to extracellular signals depends on: the receptor proteins the intracellular machinery by which it integrates and interprets the signals it receives. signal’s concentration  9 Intracellular Receptor Signal molecules: small molecules (CO, NO), hydrophobic molecules: estrogen, progesterone, testosterone, retinoic acid, vitamin D receptor: in cytoplasm or nucleus Intracellular receptor without ligand  inactive  10 Extracellular receptor Signal : Protein, berat molekul besar, hidrofilik Terjadi transduksi sinyal Amplifikasi sinyal - second messenger  11 Relay signals from cell surface Relay signals from cell surface via : 1. Small molecules : second messenger  12 Intracellular Mediators and Enzymatic Cascades Amplify Extracellular Signals  13 Two important Molecular switches Phosphorylation : protein kinase & protein phosphatase GDP/GTP binding GTPase-activating proteins (GAPs) & guanine nucleotide exchange factors (GEFs)  14 Desensitization of a signal Figure 15–21 Some ways in which target cells can become adapted (desensitized) to an extracellular signal molecule (Molecular Biology of the Cell 7/e (© Norton & Company 2022)  15 3 types of Cell-Surface Receptor Proteins Ion-channel-coupled receptors, transmitter-gated ion channels or ionotropic receptors, G-protein-coupled receptors act by indirectly regulating the activity of a separate plasma-membrane- bound target protein, which is generally either an enzyme or an ion channel. Enzyme-coupled receptors either function directly as enzymes or associate directly with enzymes that they activate  16 Signalling through GPCR GPCR ~ GEF GPCR-ligand  Activate Trimeric G proteins (3 subunits: α,β,γ) In animals: transmit extracellular signals, such as hormones, neurotransmitters, chemokines, lipid mediators, light, tastes and odorants movements G-α-subunit of G-trimeric protein bind to a specific regulator of G protein signaling (RGS). RGS ~ GAPs  17 Adenylyl cyclase activation and inhibition  18 RGS : Enzyme which catalyzed second messenger production: Adenylyl cyclase Phospholipase C-β (PLC- β) Ion channel protein  19 Figure 15-39 Molecular Biology of the Cell (© Garland Science 2008)  20 Some GPCR regulate ion channels Glutamate, serotonin and nicotinic acetylcholine receptors  ion channel coupled receptors on skeletal muscle and nerve cells GPCR activation  activate/inactivate ion channel  potential membrane  21 GPCRs regulate cyclic-Nucleotide-Gated Ion Channels In specialized olfactory receptor neurons In rod photoreceptors in vertebrate retina  22 3 types of Cell-Surface Receptor Proteins Ion-channel-coupled receptors, transmitter-gated ion channels or ionotropic receptors, G-protein-coupled receptors act by indirectly regulating the activity of a separate plasma-membrane- bound target protein, which is generally either an enzyme or an ion channel. Enzyme-coupled receptors either function directly as enzymes or associate directly with enzymes that they activate ENZYME-COUPLED RECEPTORS  24 Receptor tyrosine kinases (RTK) ligand binding causes dimerization of two molecules Activation and cross- phosphorylation each other on multiple tyrosines, a process referred to as transautophosphorylation  MAP Kinase Signaling Module three components of MAP kinase module (in mammalian:Ras-MAP-kinase signaling pathway  are all protein kinases. MAP kinase kinase (MAPKK) MAP kinase kinase kinase (MAPKKK) MAPK Figure 15-60 Molecular Biology of the Cell (© Garland Science 2008) Scaffold Proteins Help Prevent Cross- Talk Between Parallel MAP Kinase Modules  26 parallel intracellular signaling pathways activated by GPCRs & RTKs