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Transcript
Local regulators – in the vicinity Chapter 11 a. Paracrine signaling – nearby Cell Communication Cells are acted on by signaling Cell (ie. Growth factor) b. Synaptic signaling-neurotransmitters cross the synapse (gap) Between nerve cell and target Long Distance Signaling • Hormones –Endocrine signaling –Plant growth regulators Figure 11.4 Plasma membranes Gap junctions between animal cells (a) Cell junctions (b) Cell-cell recognition Plasmodesmata between plant cells Figure 11.5 Local signaling Long-distance signaling Target cell Secreting cell Local regulator diffuses through extracellular fluid. (a) Paracrine signaling Electrical signal along nerve cell triggers release of neurotransmitter. Endocrine cell Neurotransmitter diffuses across synapse. Secretory vesicle Target cell is stimulated. Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (b) Synaptic signaling (c) Endocrine (hormonal) signaling The Three Stages of Cell Signaling: A Preview –Reception –Transduction –Response © 2011 Pearson Education, Inc. Receptors in the Plasma Membrane • There are three main types of membrane receptors –G protein-coupled receptors –Receptor tyrosine kinases –Ion channel receptors © 2011 Pearson Education, Inc. ligand-gated ion channel receptor • acts as a gate when the receptor changes shape • signal molecule binds as a ligand to the receptor • the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor © 2011 Pearson Education, Inc. Figure 11.7d 1 Signaling molecule (ligand) 3 2 Gate closed Ligand-gated ion channel receptor Ions Plasma membrane Gate closed Gate open Cellular response G-protein-coupled receptor (GPCRs • works with the help of a G protein • The G protein acts as an on/off switch • If GDP is bound to the G protein, the G protein is inactive © 2011 Pearson Education, Inc. Figure 11.7b Plasma membrane G protein-coupled receptor CYTOPLASM 1 Activated receptor Signaling molecule Inactive enzyme GTP GDP GDP Enzyme G protein (inactive) 2 GDP GTP Activated enzyme GTP GDP Pi 3 Cellular response 4 • Receptor tyrosine kinases (RTKs) • membrane receptors that attach phosphates to tyrosines • can trigger multiple signal transduction pathways at once • Abnormal functioning of RTKs is associated with many types of cancers © 2011 Pearson Education, Inc. Figure 11.7c Signaling molecule (ligand) Ligand-binding site helix in the membrane Signaling molecule Tyrosines CYTOPLASM Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) 1 Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer 2 Activated relay proteins 3 Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P 6 ATP Activated tyrosine kinase regions (unphosphorylated dimer) 6 ADP Fully activated receptor tyrosine kinase (phosphorylated dimer) 4 Inactive relay proteins Cellular response 1 Cellular response 2 Intracellular Receptors • found in the cytosol or nucleus of target cells • Small or hydrophobic chemical messengers can 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 genes © 2011 Pearson Education, Inc. • 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 receptor © 2011 Pearson Education, Inc. Figure 11.7d 1 Signaling molecule (ligand) 3 2 Gate closed Ligand-gated ion channel receptor Ions Plasma membrane Gate closed Gate open Cellular response Intracellular Receptors • 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 genes © 2011 Pearson Education, Inc. Figure 11.9-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Signal Transduction Pathways • mostly proteins • Produces a domino affect • At each step, the signal is transduced into a different form, usually a shape change in a protein © 2011 Pearson Education, Inc. Protein Phosphorylation and Dephosphorylation • Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation • Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation © 2011 Pearson Education, Inc. Figure 11.10 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi P Active protein kinase 2 PP Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response Figure 11.10a Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP P Active protein kinase 2 PP Pi Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cyclic AMP • Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal • Cholera – regulating G protein for salt and water secretion. No GTP to GDP stimulates more cAMP • cGMP – relaxes smooth muscles – effects of viagra © 2011 Pearson Education, Inc. Figure 11.11 Adenylyl cyclase Phosphodiesterase H2O Pyrophosphate P ATP Pi cAMP AMP Calcium Ions and Inositol Triphosphate (IP3) • Calcium is an important second messenger because cells can regulate its concentration • Lower in cytosol than extracellular (10,000x) • Active transport of Ca++ out or from cytosol to ER and mitochondria (IP3 and DAG) © 2011 Pearson Education, Inc. Figure 11.13 EXTRACELLULAR FLUID Plasma membrane ATP Ca2 pump Mitochondrion Nucleus CYTOSOL Ca2 pump ATP Key High [Ca2 ] Ca2 pump Endoplasmic reticulum (ER) Low [Ca2 ] • A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol • Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers Animation: Signal Transduction Pathways © 2011 Pearson Education, Inc. Nuclear and Cytoplasmic Responses regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus • The final activated molecule in the signaling pathway may function as a transcription factor • © 2011 Pearson Education, Inc. Figure 11.15 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA Fine-Tuning of the Response • There are four aspects of fine-tuning to consider – Amplifying the signal (and thus the response) – Specificity of the response (liver/heart) – Overall efficiency of response, enhanced by scaffolding proteins (brain) – Termination of the signal © 2011 Pearson Education, Inc. Figure 11.18 Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Activation or inhibition Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Response 4 Cell C. Cross-talk occurs between two pathways. Response 5 Cell D. Different receptor leads to a different response. Figure 11.19 Signaling molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein Concept 11.5: Apoptosis integrates multiple cell-signaling pathways • Apoptosis is programmed or controlled cell suicide • Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells • Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells © 2011 Pearson Education, Inc. Figure 11.20 2 m Apoptotic Pathways and the Signals That Trigger Them • Caspases - the main proteases that carry out apoptosis • triggered by – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum © 2011 Pearson Education, Inc.
