Cell Communication

 Cell-to-cell communication is important for multicellular organisms

Exchange of mating factors Mating Receptor a   factor a  a factor Yeast cell, mating type a Yeast cell, mating type  a/  New a/  cell

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 chemical messengers  cell junctions directly connect adjacent cells  In local signaling, animal cells may communicate by direct contact

Plasma membranes Gap junctions between animal cells Cell junctions Cell-cell recognition Plasmodesmata between plant cells

 Animals use local regulators (for short distance signals) ◦ EX: Humans: pass a note; text message; Celly; ; Facebook  Plants and animals use chemicals called hormones (for long distance)

Paracrine signaling Local regulator diffuses through extracellular fluid Secretory vesicle Secreting cell Target cell Local signaling Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Endocrine cell Blood vessel Long-distance signaling Hormone travels in bloodstream to target cells Synaptic signaling Target cell is stimulated Hormonal signaling Target cell

 communication communication

 Earl Sutherland discovered how the hormone epinephrine acts on cells  /ch11/InstructorResources/medialib_tab_2/1.htm /ch11/InstructorResources/medialib_tab_2/1.htm

◦ Reception ◦ Transduction ◦ Response ◦ mm2/ch11/InstructorResources/medialib_tab_2/2.htm mm2/ch11/InstructorResources/medialib_tab_2/2.htm

EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule

EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule Relay molecules in a signal transduction pathway

EXTRACELLULAR FLUID Reception Plasma membrane Transduction CYTOPLASM Receptor Signal molecule Relay molecules in a signal transduction pathway Response Activation of cellular response

 The binding between a signal molecule (ligand) and receptor is specific  A conformational (shape) change in a receptor starts the process  Most signal receptors are plasma membrane proteins

 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

EXTRACELLULAR FLUID Plasma membrane The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormone- receptor complex enters the nucleus and binds to specific genes. The bound protein stimulates the transcription of the gene into mRNA. The mRNA is translated into a specific protein. CYTOPLASM NUCLEUS DNA Hormone (testosterone) Receptor protein Hormone- receptor complex mRNA New protein

 DqQo (bozeman signal transduction) DqQo

 Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane  There are three main types of membrane receptors: 1.G-protein-linked receptors 2.Receptor tyrosine kinases 3.Ion channel receptors

 A G-protein-linked receptor is a plasma membrane receptor that 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

Segment that interacts with G proteins Signal-binding site G-protein-linked receptor

 Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines  A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

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

 An 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 Ca 2+, through a channel in the receptor

Signal molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate closed Gate open Cellular response

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 Transduction usually involves multiple steps  Multistep pathways can amplify a signal: A few molecules can produce a large cellular response

 The molecules that relay a signal from receptor are mostly proteins  Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated

 In many pathways, the signal is transmitted by a cascade of protein phosphorylations  Turning activities on and off

Signal molecule Activated relay molecule Receptor Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 Active protein kinase 2 Inactive protein kinase 3 Active protein kinase 3 ADP Inactive protein Active protein Cellular response Phosphorylation cascade ATP PP P i ADP ATP PP P i ADP ATP PP P i P P P

 Second messengers are small, nonprotein, water-soluble molecules or ions ◦ The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger” ◦ Second messengers can spread through cells by diffusion ◦ Second messengers are important in G-protein-linked receptors and tyrosine kinases

Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal

ATPCyclic AMPAMP Adenylyl cyclase Pyrophosphate PP i Phosphodiesterase H2OH2O

 Many signal molecules trigger formation of cAMP

cAMP ATP Second messenger First messenger (signal molecule such as epinephrine) G-protein-linked receptor G protein Adenylyl cyclase Protein kinase A Cellular responses GTP

 Calcium ions (Ca 2+ ) act as a second messenger in many pathways  Calcium is an important second messenger because cells can regulate its concentration

ATP EXTRACELLULAR FLUID ATP Mitochondrion Ca 2+ pump Plasma membrane CYTOSOL Endoplasmic reticulum (ER) Ca 2+ pump Ca 2+ pump High [Ca 2+ ] Key Nucleus Low [Ca 2+ ]

CYTOSOL Ca 2+ Endoplasmic reticulum (ER) IP 3 -gated calcium channel IP 3 (second messenger) DAG PIP 2 G-protein-linked receptor Phospholipase C G protein Signal molecule (first messenger) EXTRACELLULAR FLUID GTP

CYTOSOL Ca 2+ Endoplasmic reticulum (ER) IP 3 -gated calcium channel IP 3 (second messenger) DAG PIP 2 G-protein-linked receptor Phospholipase C G protein Signal molecule (first messenger) EXTRACELLULAR FLUID GTP Ca 2+ (second messenger)

CYTOSOL Ca 2+ Endoplasmic reticulum (ER) IP 3 -gated calcium channel IP 3 (second messenger) DAG PIP 2 G-protein-linked receptor Phospholipase C G protein Signal molecule (first messenger) EXTRACELLULAR FLUID GTP Ca 2+ (second messenger) Various proteins activated Cellular re- sponses

Binding of epinephrine to G-protein-linked receptor (1 molecule) Reception Transduction Inactive G protein Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2 ) ATP Cyclic AMP (10 4 ) Inactive protein kinase A Inactive phosphorylase kinase Active protein kinase A (10 4 ) Active phosphorylase kinase (10 5 ) Active glycogen phosphorylase (10 6 ) Inactive glycogen phosphorylase Glycogen Response Glucose-1-phosphate (10 8 molecules)

GENE REGULATION :  Many other signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus  The final activated molecule may function as a transcription factor

Reception Growth factor Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response Gene mRNA DNA NUCLEUS

Signal molecule Receptor Relay molecules Response 1 Response 2Response 3 Cell B. Pathway branches, leading to two responses Cell A. Pathway leads to a single response Cell C. Cross-talk occurs between two pathways Response 4 Response 5 Activation or inhibition Cell D. Different receptor leads to a different response

LE Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases

LE Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases

 Inactivation mechanisms are an essential aspect of cell signaling  When signal molecules leave the receptor, the receptor reverts to its inactive state

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