BISC 307L 1st Edition Lecture 5 Cell Communication CH 6 Cellular Communication Slide 1 o Chemicals can be used as signals 1 Endocrine signaling Goes through the blood Hormones 2 Paracrine Same as endocrine but affects cells in the area 3 Autocrine The cell that sent the signal is the one that receives it 4 Pheromone Affects cell in another individual 5 Contact dependent 6 Synaptic transmission 7 Gap junctional coupling Mechanisms of hormone action Slide 2 o 1 Hydrophilic hormones water soluble cannot cross membrane need plasma membrane receptor to carry across the plasma membrane 1 Peptides 2 Proteins 3 Amines o 2 Lipophillic hormones not water soluble can cross the membrane carrier proteins in the plasma to transport around The most abundant protein in the plasma is albumin 1 Steroids 2 Thyroid o Plasma membrane receptors Lipophillic hormone Use intracellular messengers to alter enzymes channels or gene expression Recently discovered previously unknown pathway Signal Transduction Slide 3 o o Where it says proteins kinases that also includes phosphatases o Shows the general mechanism of signal transduction summary o How does this amplify the signal A single molecule binding to a receptor can cause a response because of amplification Types of Membrane receptors 4 Slide 4 o 1 Ligand gated ion channels o 2 Receptor enzymes o 3 G protein coupled progesterone membrane receptor is this type o 4 Integrin receptors Ionic Basis of Resting Membrane potential Slide 5 o o o o o o o o 1 Na K ATPase creates ionic concentration gradients 2 Membrane selectively permeable to K due to open K channels 3 K diffuses outward down the concentration gradient 4 Since Na and Cl cannot move to compensate inside becomes negative 5 K diffuses inward down its electrical gradient 6 System comes to equilibrium when flux of K out Flux of K in 7 Na and Cl are not in equilibrium 8 Electrochemical gradients especially for Na represent stored potential energy o 9 Under condition 6 The resting voltage potential Vm RT zF ln K out K in Three things to remember 1 Na K important low concentration of Na inside the cell and high concentration of K inside the cell Pump 2 Resulting distribution of ions 3 Almost all cells have open K selective ion channels in their membranes Almost all animal cells have the inside negative compared to the outside 1 Ligand Gated Ion Channels Slide 6 o K selective channel Leaky Open all the time Not gated generating resting membrane potential Called a leakage ion channel Almost all animal cells have this They actually do have gates but ALWAYS OPEN o Ligand gated Na channel The gate can either plug up the channel or not Can be ligand gated voltage gated and mechanically gated Ligand binding Na influx change in membrane potential the resulting change in voltage sensitive protein or Ca2 sensitive protein causes cellular response Neurotransmitters hormones are some examples of ligands Normally closed until ligand binds 2 Receptor Enzymes Slide 7 o the receptor is an enzyme o most important is the RECEPTOR TYROSINE KINASE Trk bind a pair of ligand molecules exist as monomers but when they attach to two ligands this dimerizes them making them active auto phosphorylation binding of accessory proteins activation of multiple signal transduction pathways 3 G Protein coupled receptors Slide 8 o Neurotransmitter binds receptor makes it possible for the G protein to bind to the intracellular side of the e receptor and this turns the GDP protein to GTP and this activates Adenylyl cyclase synthesis of cAMP from ATP o Called a stimulatory G protein o Inactivation happens when GTP is hydrolyzed to GDP G protein coupled receptors part 2 Slide 9 o Inhibitory g proteins also can inhibit cAMP production o G proteins can activate and inhibit o inhibited by phosphodiesterase which will continue the production of cAMP o multiple control DAG IP3 System Slide 10 G protein continued o Example of G protein system The enzyme that gets activated is Phospholipase C and the substrate for this is membrane lipids Metabolizes phosphatidyl inositol which is made into Diacylgycererol Can be metabolized to form a soluble Arachidonic acid Or can activate protein kinase C calcium dependent which in the presence of sufficient amount of Ca2 creates a cellular response IP3 acts in two different ways 1 IP3 binds to IP3 gated Ca2 channels IP3 is the ligand for the Ca2 channels in endoplasmic reticulum so when it binds it lets the Ca2 out which can bind to CaM kinase which causes cellular response 2 Can be converted to IP4 enhances Ca2 channels in plasma membrane increases Ca2 influx can act as a second messenger this Ca2 that enters from the outside of the cell is new Ca2 to cell so it replenishes Ca2 stores inside the cell smooth muscle and cardiac muscle this is important Arachidonic Acid System Slide 11 o Can come from 1 the metabolism of diacylglycerol 2 a ligand deactivating a G protein coupled receptor o Importance Has second messenger activity itself Serves as a substrate for the synthesis of a wide variety of 20 carbon eicosanoids These are lipid soluble and there are a lot of them Three major categories of lipid soluble paracrines 1 Prostaglandins from COX 1 2 Thromboxanes from COX 2 o mediating vasodilation in the lings and cardiac muscle o regulation of blood pressure o released in injury o signal pain o Prostaglandins have the same function o COX 1 inhibitors Drugs that inhibit these molecules are called non steroidal anti inflammatory drugs NSAIDS ibuprofen Aleve aspirin Can lead to stomach bleeding due to COX 1 o COX 2 inhibitors Vioxx Celebrex Don t cause bleeding 3 Leukotrienes from lipoxygenase o important signaling molecules o important role in asthma o used by white blood cells 4 Integrin Receptors Slide 12 o Don t need to know about these o Membrane bound receptors o Non soluble lipids are the ligands on the outside o On the inside they bind to the cytoskeleton o Link insoluble ECM ligands to insoluble ICM proteins o Many of the effects of integrin receptors is due to their binding to actin on the inside of the cell o Integrin exists as a heterodimer 2 subunits that aren t identical o In absense of the ligand these dimers are separate in the membrane and are mobile but when ligand is present these diners become clustered o What do they do Blood clotting Wound healing Recognition by immune system of specific molecules Cell adhesion Cell movement Important for immune system Gaseous Signal Molecules NO CO and H2S Slide