PJ1311 Lecture 3 - Cell Communication PDF

The Human Body PJ1311 Lecture 3: Cell Communication Dr Alina Oknianska  Learning Objectives and Exam Revision Advice You should be able to discuss different classes of cell surface receptors and principles of signalling via intracellular receptors You should be ab...

The Human Body PJ1311 Lecture 3: Cell Communication Dr Alina Oknianska  Learning Objectives and Exam Revision Advice You should be able to discuss different classes of cell surface receptors and principles of signalling via intracellular receptors You should be able to characterise four main ways to send signals between cells Endocrine Paracrine Neuronal Contact dependent  Introduction Cells must respond to changes in external environment Adaptation In multicellular organisms – also receive signals from other cells Coordinate behaviour Understand how cells send and receive signals  General Principles of Cell Signalling Information in variety of forms – often need to convert from one form to another Signal transduction process of converting signal  General Principles of Cell Signalling Typical cellular communication Signalling cell produces a signal molecule Signal molecule detected by receptor protein on target cell  Signals can Act over a Long or Short Range 100s different extracellular signal molecules Proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, dissolved gases Four main ways to send signals between cells Endocrine Paracrine Neuronal  Signals can Act over a Long or Short Range : Endocrine Hormones produced in endocrine glands distributed throughout the body  Signals can Act over a Long or Short Range : Paracrine Signals released by cells into extracellular fluid – act locally  Signals can Act over a Long or Short Range : Neuronal Neuronal signals are transmitted along axons to remote target cells  Signals can Act over a Long or Short Range : Contact-Dependent Cell-surface-bound signal molecule binds to receptor protein on adjacent cell  Each Cell Responds to a Limited Set of Signals Depending on History and Current State A cell in a multicellular organism exposed to 100s of different signalling molecules Cells must select which signals to respond to Depends on presence of receptor protein Each receptor usually activated by one type of signal Without appropriate receptor – no response Limits the signals cell will respond to  Each Cell Responds to a Limited Set of Signals Depending on History and Current Each receptor usually State activated by one type of signal Response Response Response  Each Cell Responds to a Limited Set of Signals Depending on History and Current State Every cell type: set of receptor proteins Respond to specific set of extracellular signalling molecules Signalling molecules work in combination to regulate  Extracellular Signalling Molecules Two classes of extracellular signalling molecules Cell Surface Receptors Relay Extracellular Signals Via Intracellular Signalling Pathways Signal from cell surface receptor transmitted into target cell by intracellular signalling molecules Ultimately alter activity of effector protein Cell Surface Receptors Relay Extracellular Signals Via Intracellular Signalling Pathways Intracellular signalling proteins can relay, amplify, integrate and distribute incoming signal Some Intracellular Signalling Proteins Act as Molecular Switches Molecular switches – turned on or off Ensures proteins can be reset Two classes of switches Additional/removal of phosphate group – phosphorylation Whether bound to GTP or GDP – GTP binding proteins Some Intracellular Signalling Proteins Act as Molecular Switches Two classes of switches Cell Surface Receptors Fall into Three Main Classes  Cell Surface Receptors Fall into Three Main Classes : Ion–Channel Coupled Receptors Opens (or closes) in response to binding of signalling molecule Allows flow of ions across membrane Changes membrane potential and produces an electrical current  Cell Surface Receptors Fall into Three Main Classes : Ion–Channel Coupled Receptors Specialty of nervous system and other electrically excitable cells such as muscle cells. Rapid transmission of signals across synapses in NS.  Cell Surface Receptors Fall into Three Main Classes : Ion–Channel Coupled Acetylcholine most Receptors common neurotransmitter Acetylcholine receptor – ligand-gated sodium channel binds 2 molecules of acetylcholine to open.  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Receptor Receptors binds signalling molecule Activated receptor signals GTP binding protein (G protein) on inside of plasma membrane Either switches on (or off) an enzyme or ion channel Initiates cascade of events  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Receptors Receptor and G protein inactive (bound GDP) Binding of signalling molecule to receptor Activates G protein – GDP exchanged for GTP Interact with target proteins  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Receptors Most frequent target for G proteins are the enzymes Adenylyl cyclase Phospholipase C Make second messengers – small intracellular signalling molecules  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Adenylyl Receptors cyclase makes cyclic AMP (cAMP) cAMP levels increase rapidly in response to extracellular signal  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Receptors cAMP often activates cyclic AMP dependent protein kinase (PKA) Downstream effects E.g. glycogen breakdown in skeletal muscle  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Receptors Cellular responses mediated by cAMP  Cell Surface Receptors Fall into Three Main Classes : Phospholipase G–Protein–Coupled Receptors C makes inositol trisphosphate (IP3) and diacylglycerol (DAG)  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Phospholipase Receptors C activates two signalling pathways  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Increase Receptors in calcium levels triggers many biological processes E.g. fertilisation of egg by sperm – initiates embryonic development  Cell Surface Receptors Fall into Three Main Classes : G–Protein–Coupled Receptors Cellular responses mediated by phospholipase C activation Cell Surface Receptors Fall into Three Main Classes  Cell Surface Receptors Fall into Three Main Classes : Enzyme–Coupled Receptor Receptors binds signalling molecule – enzyme activity is switched on inside cell Receptor own enzyme activity or associates with enzymes Activate variety of intracellular signalling pathways  Cell Surface Receptors Fall into Three Main Classes : Enzyme–Coupled Receptors Largest group is receptor tyrosine kinases (RTKs) Binding of signalling molecule to extracellular domain of RTKs – dimerisation Causes close associated of intracellular kinase domains Activation of kinases – phosphorylate each other on tyrosine residues Binding and activation site for other  Cell Surface Receptors Fall into Three Main Classes : Enzyme–Coupled Receptors Activation of RTKs stimulates assembly of intracellular signalling complex  Cell Surface Receptors Fall into Three Main Classes : Most RTKs Enzyme–Coupled Receptors activate the monomeric GTPase Ras RTKs recruit Ras-activating protein – causes Ras to exchange GDP (off) for GTP (on)  Cell Surface Receptors Fall into Three Main Classes : Ras activates Enzyme–Coupled Receptors a MAP-kinase signalling module Cell Surface Receptors are often Targets for Chemicals  Extracellular Signalling Molecules Two classes of extracellular signalling molecules  Some Hormones Can Cross the Plasma Membrane and Bind Intracellular Receptors Steroid hormones, important class of signalling molecule – rely on intracellular receptors Hydrophobic molecules – pass through plasma membrane Bind to intracellular receptors and activates located either in cytoplasm or nucleus Affects transcription of target genes  Some Hormones Can Cross the Plasma Membrane and Bind Intracellular Receptors Steroid hormone cortisol is produced by adrenal glands in response to stress Biological affect – mainly metabolic  Summary Cells in multicellular organisms communicate through large variety of extracellular signals Extracellular signalling molecules bind to and activate receptor proteins on the target cell Cell-surface and intracellular receptors  Summary Cell surface receptors are divided into 3 classes: ion-channel-coupled G-protein-coupled (GPCRs) Enzyme coupled receptors e.g. RTKs