Long-distance signaling

Long-distance signaling
Chapter 11: Cell Communication What is the difference between paracrine signaling & endocrine signaling? Paracrine – local signaling from 1 cell to another in close range Endocrine – long-distance signaling involving hormones (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood Hormones may reach virtually all body cells. Local regulator diffuses through extracellular fluid Secreting cell Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling Long-distance signaling Endocrine cell Blood vessel Target

Figure 11.3 Communication by direct contact between cells
Plasma membranes (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Plasmodesmata between plant cells Gap junctions between animal cells

Chapter 11: Cell Communication
What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor EXTRACELLULAR FLUID Receptor Signal molecule Plasma membrane CYTOPLASM Reception Transduction 1 2

Relay molecules in a signal transduction pathway
Chapter 11: Cell Communication What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response EXTRACELLULAR FLUID Receptor Signal molecule Plasma membrane CYTOPLASM Reception Transduction 1 2 Relay molecules in a signal transduction pathway

Chapter 11: Cell Communication What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response Response – cell’s response to the signal EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Reception Transduction Response 1 2 3

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What are the 4 types of receptors? Intracellular receptors…..aka steroid hormone receptors G-protein-linked receptors Tyrosine kinase receptors Ligand-gated ion channels membrane-bound (integral proteins)

Fig. 11.6 Steroid hormone interacting with an intracellular receptor
(testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM New protein The non-polar steroid hormone testosterone passes through the plasma membrane. 1 Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3 The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What are the 4 types of receptors? Intracellular receptors…..aka steroid hormone receptors G-protein-linked receptors Associated with a cytoplasmic G-protein G-protein binds either GDP (inactive) or GTP (active) Ligand binding Causes a change in receptor shape which Attracts the inactive G-protein GTP displaces GDP activating the G-protein Activated G-protein can then activate other specific molecules G-proteins have GTPase activity to hydrolyze & inactivate G-protein

Figure 11.7 Exploring Membrane Receptors
Signal-binding site G-PROTEIN-LINKED RECEPTORS G-protein-linked receptor Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated receptor Signal molecule Inactive Segment that interacts with G proteins GDP GTP P i

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What are the 4 types of receptors? Intracellular receptors…..aka steroid hormone receptors G-protein-linked receptors Tyrosine kinase receptors Kinase – enzyme that phosphorylates Ligand binding Causes receptor to form a dimer Cytoplasmic tails phosphorylate each other ATP is hydrolyzed & terminal phosphate is added to tyrosine aa Activated receptors can then activate specific relay proteins

RECEPTOR TYROSINE KINASES
Signal molecule Signal-binding site CYTOPLASM Tyrosines Signal molecule  Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated 6 ATP ADP

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What are the 4 types of receptors? Intracellular receptors…..aka steroid hormone receptors G-protein-linked receptors Tyrosine kinase receptors Ligand-gated ion channels Ligand binding Causes a change in shape Allows specific ions to move down concentration gradient e.g. neurotransmitters between neurons

ION CHANNEL RECEPTORS Gate Closed Gate close Signal molecule (ligand)
Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellular response Gate close

Chapter 11: Cell Communication What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response EXTRACELLULAR FLUID Receptor Signal molecule Plasma membrane CYTOPLASM Reception Transduction 1 2 Relay molecules in a signal transduction pathway

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response Often done by protein phosphorylations Protein kinases phosphorylate other relay molecules (kinases) Inactivated by phosphatases

Figure 11. 8 A phosphorylation cascade
Figure 11.8 A phosphorylation cascade (involves several protein kinases) Signal molecule Active protein kinase 1 2 3 Inactive protein kinase Cellular response Receptor P P ATP ADP PP Activated relay molecule A relay molecule activates protein kinase 1. Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5 i Phosphorylation cascade

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response Often done by protein phosphorylations 2nd messengers cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP O –O N O P OH CH2 NH2 ATP Ch2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i

Fig 11.10 cAMP as a second messenger in a G-protein-signaling pathway
First messenger (signal molecule such as epinephrine) ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein Second messenger

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response Often done by protein phosphorylations 2nd messengers cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP Ca+2 ions Released from ER Muscle contractions Cell division

Figure 11.11 Maintenance of calcium ion concentrations in an animal cell
EXTRACELLULAR FLUID Plasma membrane ATP CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [Ca2+] Low [Ca2+]

Figure 11.12 Calcium and IP3 in signaling pathways
How does Ca+2 get released from the ER? - more 2nd messengers - IP3 - follow the numbers IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 IP3 (second messenger) DAG 3 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Endoplasmic reticulum (ER) Phospholipase C PIP2 GTP Ca2+ IP3-gated calcium channel A signal molecule binds to a receptor, leading to activation of phospholipase C. 1 2 CYTOSOL

IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Endoplasmic reticulum (ER) Phospholipase C PIP2 IP3 (second messenger) DAG GTP Ca2+ (second messenger) IP3-gated calcium channel DAG functions as a second messenger In other pathways. CYTOSOL Calcium ions flow out of the ER (down their concentration gradient), raising the Ca2+ level in the cytosol. 5

IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 The calcium ions activate the next protein in one or more signaling pathways. 6 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca2+ level in the cytosol. 5 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP2 IP3 (second messenger) DAG Cellular responses GTP Ca2+ (second messenger) IP3-gated calcium channel A signal molecule binds to a receptor, leading to activation of phospholipase C. 1 CYTOSOL 2 3

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? Reception – ligand (signal molecule) binding to a receptor Transduction – conversion of the received signal to a specific cellular response Often done by protein phosphorylations Protein kinases phosphorylate other relay molecules (kinases) Inactivated by phosphatases 2nd messengers cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP Ca+2 ions IP3 - inositol triphosphate DAG – diacyl glycerol Response – cell’s response to the signal What is meant by signal amplification? A single ligand can activate millions of molecules during a cell’s response

Binding of epinephrine to G-protein-linked receptor (1 molecule)
Figure 11.13 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Glucose-1-phosphate (108 molecules) Glycogen Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Active phosphorylase kinase (105) Inactive phosphorylase kinase Inactive protein kinase A Active protein kinase A (104) ATP Cyclic AMP (104) Active adenylyl cyclase (102) Inactive adenylyl cyclase Inactive G protein Active G protein (102 molecules) Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Response Reception - Cytoplasmic signal amplification

Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor
Nuclear signal amplification Growth factor Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive DNA Phosphorylation cascade CYTOPLASM Receptor

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What is meant my signal amplification? How can cells have different responses to the same signal? Different relay proteins Cross-talk w/ diff. signals Different receptor types Response 1 Response 4 Response 5 Response 2 Response 3 Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response Activation or inhibition Receptor Relay molecules Signal molecule

What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What is meant my signal amplification? How can cells have different responses to the same signal? How do scaffolding proteins help cell communication? - By binding several different molecules together for quicker process Signal molecule Receptor Scaffolding protein Three different protein kinases Plasma membrane

Long-distance signaling

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