Cell Communication - Chapter 11 (PDF)

Chapter 11 Cell Communication  Overview: The Cellular “Internet” Cell-to-cell communication is essential for multi- cellular organisms universal mechanisms of cellular regulation The combined effects; multiple signals – determine cell response Example: the dilation of blood ve...

Chapter 11 Cell Communication  Overview: The Cellular “Internet” Cell-to-cell communication is essential for multi- cellular organisms universal mechanisms of cellular regulation The combined effects; multiple signals – determine cell response Example: the dilation of blood vessels is controlled by multiple molecules (NO, Epi, ACh, etc.)  Basic Signaling Mechanisms Juxtacrine Autocrine/Paracrine Neural Endocrine A visual explanation…. Figure 11.4 Plasma membranes Cell wall Gap junctions Plasmodesmata between animal cells between plant cells (a) Cell junctions JUXTACRINE (b) Cell-cell recognition Figure 11.5 Local signaling Target cells Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across Secreting synapse. cell Secretory vesicles Local regulator Target cell (a) Paracrine signaling (b) Synaptic signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel (c) Endocrine (hormonal) signaling  The Three Stages of Cell Signaling: Earl W. Sutherland – discovered how the hormone epinephrine acts on cells Nobel Prize (1971) Sutherland suggested that cells receiving signals went through three processes: – Reception – Transduction – Response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Figure 11.6-1 EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception Receptor Signaling molecule Figure 11.6-2 EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction Receptor 1 2 3 Relay molecules Signaling molecule Figure 11.6-3 EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation 1 2 3 of cellular response Relay molecules Signaling molecule  Reception: LIGAND Receptors are proteins (tertiary structure???) Where could receptors be found? – Intracellular vs. plasma membrane What quality must a molecule have in order to pass through the membrane and bind intracellular receptors? Fig. 11-8-1 Hormone EXTRACELLULAR (testosterone) FLUID Plasma membrane Receptor protein DNA NUCLEUS CYTOPLASM Fig. 11-8-2 Hormone EXTRACELLULAR (testosterone) FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-3 Hormone EXTRACELLULAR (testosterone) FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-4 Hormone EXTRACELLULAR (testosterone) FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM Fig. 11-6-1 EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception Receptor Signaling molecule Fig. 11-6-2 EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Fig. 11-6-3 EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule  Membrane Receptors Many classes – Ligand gated ion channels Nicotinic receptor found in skeletal muscle – Cytokine receptors (not in book) – Receptor Tyrosine Kinases – G-Protein Coupled Receptors (GPCR) Figure 11.8d-1 1 Gate Ions Signaling closed molecule (ligand) Ligand gated ion channel… Plasma Ligand-gated membrane ion channel receptor Figure 11.8d-2 1 2 Gate Gate open Ions Signaling closed molecule (ligand) Plasma Cellular Ligand-gated response membrane ion channel receptor Figure 11.8d-3 1 2 Gate Gate open Ions Signaling closed molecule (ligand) Plasma Cellular Ligand-gated response membrane ion channel receptor 3 Gate closed Figure 11.8c Signaling molecule Signaling molecule (ligand) Ligand-binding site  helix in the membrane Tyr Tyr Tyr Tyr Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine Dimer kinase proteins CYTOPLASM (inactive monomers) 1 2 TYROSINE KINASE RECEPTORS GROWTH FACTORS are linked to Activated relay proteins Cellular P Tyr P Tyr Tyr P Tyr Tyr Tyr P response 1 Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular 6 ATP 6 ADP response 2 Activated tyrosine Fully activated kinase regions receptor tyrosine (unphosphorylated kinase (phos- Inactive dimer) phorylated dimer) relay proteins 3 4 Mutations and receptor activation: Cytokine Receptors Figure 11.8a Signaling molecule binding site Segment that interacts with G proteins G protein-coupled receptor Figure 11.8b Signaling Inactive G protein-coupled Plasma membrane Activated molecule enzyme receptor receptor GTP GDP GDP G protein GTP CYTOPLASM GDP (inactive) Enzyme 1 2 Activated enzyme GTP GDP Pi Cellular response 3 4  Transduction: Signal transduction – Generally multiple steps – Many steps can amplify a signal: – BENEFIT??? opportunities for coordination/regulation of the cellular response What molecule(s) carry the message from the cell membrane receptor to the intracellular compartment?  Second Messengers The LIGAND = “first messenger” Second messengers – small, non-protein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers – Play a role in G protein-coupled receptors and receptor tyrosine kinases – EXAMPLES: Cyclic AMP, cyclic GMP, IP3, DAG and calcium ions Fig. 11-10 Adenylyl cyclase Phosphodiesterase Pyrophosphate P Pi ATP cAMP AMP **role of phosphodiesterases Fig. 11-11 First messenger Adenylyl G protein cyclase G protein-coupled GTP receptor ATP Second cAMP messenger Protein kinase A Cellular responses  Kinases: Enyzmes that phosphorylate a substrate – What is phosphorylation? – Adding group changes shape of protein substrate… and changing the shape of a protein alters its function – Kinase cascade… next slide Figure 11.10 Signaling molecule TAKE HOME: Receptor Activated relay molecule Kinases phosphorylate (they add a phosphate) Inactive thereby changing structure protein kinase 1 Active which changes function Ph protein os kinase p 1 ho Inactive ry protein kinase ATP la 2 ADP P tio Active protein n PP kinase ca Pi 2 sc ad Inactive protein kinase ATP e ADP P 3 Active protein PP kinase Pi 3 Inactive protein ATP P ADP Active Cellular protein response PP Pi  Calcium Ions Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration – Calcium can regulate the activity of many enzymes Affect the tertiary structure of many proteins – structural changes can alter function… Figure 11.13 Endoplasmic Plasma reticulum (ER) membrane ATP Mitochondrion Nucleus Ca2 pump ATP CYTOSOL ATP EXTRACELLULAR FLUID Key High [Ca2 Low [Ca2 Second messengers to this point… cAMP (from ATP) – Activates protein kinase Calcium – Regulates MANY enzymes/processes in cell cGMP (from???) – GTP precursor; activates a DIFFERENT protein kinase than cAMP And, finally… Figure 11.14-1 EXTRA- Signaling molecule CELLULAR (first messenger) FLUID G protein GTP DAG G protein-coupled CYTOSOL receptor Phospholipase C PIP2 IP3-gated calcium channel IP3 Endoplasmic (second messenger) reticulum (ER) lumen Ca2 Nucleus Figure 11.14-2 EXTRA- Signaling molecule CELLULAR (first messenger) FLUID G protein GTP DAG G protein-coupled CYTOSOL receptor Phospholipase C PIP2 IP3-gated calcium channel IP3 Endoplasmic (second messenger) reticulum (ER) lumen Ca2 Ca2 Nucleus (second messenger) Figure 11.14-3 EXTRA- Signaling molecule CELLULAR (first messenger) FLUID G protein GTP DAG G protein-coupled CYTOSOL receptor Phospholipase C PIP2 IP3-gated calcium channel IP3 Endoplasmic (second messenger) reticulum (ER) lumen Ca2 Various Cellular proteins responses Ca2 activated Nucleus (second messenger) Figure 11.15 Growth factor Reception Receptor What happens in a cell when a signal transduction Phospho- rylation cascade is turned on… cascade Transduction CYTOPLASM Inactive Active transcription transcription factor factor Response P DNA Gene NUCLEUS mRNA  Fine-Tuning of the Response Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response  Signal Amplification Enzyme cascades amplify the cell’s response At each step, the number of activated products is much greater than in the preceding step – How??? Figure 11.16 Reception Transduction Binding of epinephrine to G protein-coupled Inactive receptor G protein (1 molecule) Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Response Active phosphorylase kinase (105) Inactive Glycogen glycogen phosphorylase Glucose 1-phosphate Active glycogen phosphorylase (106) (108 molecules)  Fine-Tuning of the Response Not only can you have multiple steps… but you can have multiple targets AND multiple receptors… – EX: Epinephrine can bind to β1, β2, β3, α1, and α2 receptors (all are expressed in different tissues and regulate different 2nd messenger pathways – WHY is this important?? That is, what does this allow for??? Figure 11.17 Signaling molecule Receptor Relay mole- cules Activation or inhibition Response 1 Response 2 Response 3 Response 4 Response 5 Cell A: Pathway leads Cell B: Pathway Cell C: Cross-talk Cell D: Different to a single response. branches, leading to occurs between two receptor leads to a two responses. pathways. different response.  Apoptosis: Apoptosis is programmed or controlled cell suicide – Greek; “Falling off” Cell shrinks and becomes lobed (“blebbing”…. Next slide) Fig. 11-19 2 µm  Apoptosis: Apoptosis is programmed or controlled cell suicide – Greek; “Falling off” Cell shrinks and becomes lobed (“blebbing”) – cell is packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell (cells don’t LYSE like dying cells often do) WHY?  Apoptotic Pathways and the Signals That Trigger Them Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by… © 2011 Pearson Education, Inc.  What is the role of apoptosis? Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers © 2011 Pearson Education, Inc. Figure 11.22 Cells undergoing Space between Interdigital tissue apoptosis 1 mm digits