Cell communication Extracellular Intracellular Ions, water, molecules Information Control of cell function How do cells communicate with one another, and how do the signals affect cell function?Cell communication • Cell-to-cell communication is essential for multicellular organisms  The combined effects of multiple signals determine cell response • Direct exchange of materials between the cytoplasm.  Gap junctions and plasmodesmata • Direct interaction of cell surface molecules  cell adhesion.Cell communication • Indirect communication between two non-contacting cells.  A signal released from one cell that affects the function of a second • Different types of signaling depends on the distance that separates the 2 cell types. • In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances Paracrine: act on other cells Autocrine: act on itself or like cells Signaling cell Signaling cellCell communication • In long-distance signaling, plants and animals use chemicals called hormones – Endocrine Signaling cellThe Three Stages of Cell Signaling • Cells receiving signals went through three processes:  Reception  Transduction  Response • Receptor specificity  Signals (ligands) cannot alter cell function until they bind to a specific molecule - a receptor.  This interaction can be very specific • Two major receptor types:  Those located in the membrane that interact with hydrophilic signals that cannot cross the plasma membrane. • Amino acids, their derivatives, and peptides.  Those found in the cytoplasm that bind to hydrophobic signals that can cross the plasma membrane. • Steroids.Reception 1 EXTRACELLULAR FLUID Signaling molecule Plasma membrane CYTOPLASM 1 Receptor Ligand1 EXTRACELLULAR FLUID Signaling molecule Plasma membrane CYTOPLASM Transduction 2 Relay molecules in a signal transduction pathway Reception 1 ReceptorEXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response Transduction Response 2 3 Reception 1 1. Alteration of enzyme function 2. Alteration of gene expressionReception: A signal molecule binds to a receptor protein, causing it to change shape • The binding between a signal molecule (ligand) and receptor is highly specific  A shape change in a receptor is often the initial transduction of the signal • Most signal receptors are plasma membrane proteins  Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane • There are three main types of membrane receptors:  G protein-coupled receptors  Receptor tyrosine kinases  Ion channel receptorsG protein-coupled receptor • A G protein-coupled receptor (GPCR) is a plasma membrane receptor that works with the help of a G protein  An intracellular guanine nucleotide binding protein. • GTP or GDP  The G protein acts as an on/off switch. • Inactive when GDP is bound • Active when GTP is bound • Largest family of cell surface receptors.  5% of the genes in the nematode C. elegans.  Over 1000 involved in the sense of smell alone. • Signaling molecules range from proteins to small peptides, amino acid derivatives, and fatty acids. • Despite their diversity, all have the same general structure.  Span the membrane 7 times.  Called serpentine receptors.GPCR signaling Effector proteinReceptor tyrosine kinases • Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines  Can trigger multiple signal transduction pathways at once • To function they have two components:  a kinase (which is actually part of the receptor itself)  a target (or ‘relay’) protein, which is separate from the receptor • A functional receptor has two parts, which dimerize when the ligand binds.  Dimerization activates the kinase part of receptor.Receptor tyrosine kinases • The kinase moves a phosphate group from ATP to a specific amino acid located within the cytoplasmic protein  Tyrosine, serine, or threonine  Phosphorylates itself or autophosphorylation • When phosphorylated they become active and activate relay proteins, again by phosphorylation.Actions of nerve growth factor receptor TrkALigand-gated ion channels • A ligand-gated ion channel receptor acts as a gate when the receptor changes shape • When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptorIntracellular Receptors • Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells • Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors  Examples of hydrophobic messengers are the steroid and thyroid hormones of animals • An activated hormone-receptor complex can act as a transcription factor, turning on specific genesIntracellular ReceptorsIntracellular ReceptorsTransduction: Intracellular signal transduction pathways • Signal transduction pathways are cascades of intracellular events.  Triggered by the binding of the ligand to its specific receptor. • Signal transduction usually involves multiple steps  Benefits: • Can amplify a signal: A few molecules can produce a large cellular response • Provide more opportunities for coordination and regulation of the cellular response  The molecules that relay a signal from receptor to response are mostly proteins  Receptor activates another protein, which activates another, and so on  A cascadeProtein phosphorylation • At each step, the signal is transduced into a different form, usually a shape change in a protein  Addition of a phosphate will induce a conformational change. • Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation • Protein phosphatases remove the phosphates from proteins, a process called dephosphorylationProtein phosphorylation • This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and offIntracellular 2nd messengers • The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” • Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion • Second messengers