Cell signalling and receptors Cellular communication . No cell exists in isolation. · Signals must be received and processed from the environment and from other cells. · Signals are generally transmitted across the environment in the form of soluble molecules. . These molecules must be detected, and appropriate responses produced. . The biggest barrier to this process is the cell membrane. Different modes for a cell to receive stimuli a) Contact dependent (A) CONTACT-DEPENDENT signaling cell target cell membrane- bound signal molecule b) Paracri ne (B) PARACRINE signaling cell target cells local mediator (C) SYNAPTIC synapse neuron axon neurotransmitter target cell cell body d) End ocri ne e) auto crin e = self-signalling (D) ENDOCRINE endocrine cell receptor target cell hormone bloodstream target cell Cellular communication (E) AUTOCRINE = self signalling Receptor Signalling Molecule > The membrane is impermeable to large soluble molecules. > Some are transported across the membrane. > Others are detected outside of the cell and a signal transmitted into the cell. > This is the role of receptors. Receptors and ligands . Ligand" is derived from the latin ligandum meaning “binding”. . A ligand is a molecule that binds to a receptor. . For example, the ligand of the insulin receptor is insulin. · Some receptors have one ligand whilst others have many. · Different ligands can produce different responses at the same receptor e.g. agonist / antagonist. c) Synaptic
· So-called receptors communicate signals to cells · Thousands of receptors exist in humans · Detect a vast array of signals: >Dissolved gases (NO, CO, H2S) > Amino acids > Peptides/proteins > Retionoids > Fatty acids > Nucleotides The plasma membrane as interaction surface with the surrounding of a cell · Receptors are generally integral (transmembrane) proteins. · The extracellular region detects ligands. · The intracellular region interacts with effectors. Location of receptors · Receptors can be either on the cell surface or intracellular Receptors modify cellular responses by signalling cascades INTRACELLULAR RECEPTORS CELL-SURFACE RECEPTORS small hydrophobic signal molecule plasma membrane cell-surface receptor protein target cell carrier protein hydrophilic signal molecule target cell nucleus intracellular receptor protein Ligand -> ligand binding domain->receptor-> enzymatic activity in intracellular domain-> intracellular (cytoplasmic) mediators-> effector enzymes-> target proteins definitions 1 Ligand and receptor have already been defined. > Intracellular mediators - proteins that transmit the signal from the receptor to the 1 Effector enzymes - bring about changes in the cell resulting in, and affected by, production of 1 Second messengers - alter metabolism or affect effector enzymes that modulate > Target proteins - alter gene transcription and cell behaviour. > Not all signalling pathways will contain all of these components. Receptors · contain at least one binding site for a ligand · a ligand that induces a positive, physiological response is called an agonist · a ligand that represses a physiological response is called an antagonist Receptors can communicate the binding of a ligand to the cell! Ligand- gated ion channels G protein- coupled receptors Receptor tyrosine kinases Intracellular