Cell Communication Chapter 11

Cell communication

Caffeine  Sends signals to  Blood vessels  Brain  Liver  Heart

Epinephrine

Figure 11.7 Plasma membrane Cholesterol Molecule mimicking ligand β 2 -adrenergic receptors

Yeast cells

Bacteria

Cell communication  Evolution  Single cell organisms communicate.  Hallmark of multicellular organisms.  Coordinates cell behavior  Body functions as a whole.

Cell communication  Cells are exposed to a continuous stream of signals.  Signals come from the environment surrounding the cell.  Signals can be from another cell.  Chemical signals

Chemical signals  Peptides  Proteins  Amino acid  Nucleotides  Steroids or other lipids  NO or Nitric oxide

Types of cell signaling  Depend on location of cells  1. Direct contact  2. Local signaling  A. Paracrine signaling  B. Synaptic signaling  3. Long-distance signaling  Endocrine  Nerve electrical impulse

1. Direct contact  Gap junction: Animal cells  Plasmodesmata: Plant cells  Chemical or electrical impulse

1. Direct contact  Cell-cell recognition  Cells are close  Molecules on one cell are recognized by the plasma membrane of another cell.  Early development (embryonic)  Immune system

2. Local signaling  A. Paracrine signaling  Short-lived signals with local effects.  Growth factors  Early development

Local signaling  B. Synaptic signaling  Involves the nervous system  Neurotransmitters:  Signal molecules  Chemical synapse:  Communication be neuron & the target cell

Long distance Signaling  Endocrine signaling  Molecules that remain in the extracellular fluid  Enter the bloodstream  Affect cells very far from where released  Hormones:  longer-lived signal molecules

Figure 11.5c (c) Endocrine (hormonal) signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel

Long distance signaling  Nerve cell (axon)  Electrical impulse along the neuron

Signal transduction pathway  The signal causes a response in the cell

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

Signal transduction pathway  Reception:  Signal is detected  Molecule binds a receptor protein  Located on surface or inside

Signal transduction pathway  Transduction:  Signaling molecule changes receptor  Changes signal so it can cause a response  Single step  Multiple steps

Signal transduction pathway  Response:  Stimulates a specific cellular response  Activation of an enzyme  Correct cell  Correct response

Reception  Ligand:  Molecule that binds specifically to another molecule  Activates the receptor protein  Receptor protein undergoes change in shape

Reception  Most receptors are plasma membrane proteins  Signal (ligand) large, water soluble

Receptors  A. Intracellular receptors.  B. Cell surface receptors.  1. Ion-channel receptors  2. Tyrosine kinases  3. G-protein-coupled receptors

A. Intracellular receptors  Lipid-soluble signaling molecule  Small molecule  Able to cross the membrane  Interacts with a receptor inside.  Bind protein receptors in the cytoplasm  Bind protein receptors in the nucleus

A. Intracellular receptors  1. Act as regulators of gene expression  Activate or suppress expression of certain genes  Cortisol, thyroxine, testosterone, estrogen & progesterone are signal molecules.

Fig Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM

A. Intracellular receptors  2. Receptors act as enzymes  Example: NO  Binds a receptor.  Activates the enzyme to catalyze the synthesis of GMP  Relax smooth muscle  Causing blood vessels to relax  Causes an increased blood flow

B. Cell surface receptors  Many signal molecules are water soluble  Unable to pass through membrane  Bind a receptor on the surface  Causes a change inside cell.

B. Cell surface receptors  1. Ion channels  Chemically gated  Receptor proteins that allow ions to pass through  Opens only when a signal molecule (ligand) binds to receptor.  Ions are sodium, potassium, calcium or chlorine.  Gate closes when ligand is released  Example of signal molecule-neurotransmitter

2. Tyrosine Kinases  Single molecules bind receptor outside the cell  Stimulates receptor to activate the enzyme in the cytoplasm  These enzymes catalyze the transfer of phosphate groups

2. Tyrosine Kinases  Phosphorolated receptor  Addition of phosphates to receptor  Triggers a cell response  Can trigger more than one response

Fig. 11-7c Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P

3. G-protein-linked receptors  G-protein  Inactive: GDP (guanosine diphosphate)  Active: GTP (guanosine triphosphate)  Signal molecule binds the receptor  Activates the receptor  Activates the G-protein  G-protein then initiates a series of events  It can open an ion channel or stimulate an enzyme

GDP vs GTP

G-protein  It is a short lived response  Dependent on continued extracellular stimulation

Fig. 11-7b G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme

G-protein coupled receptor

Transduction  Relay of signals from receptors to target cell  Multiple steps  Amplify the signal  Coordination of simple processes

Transduction  Proteins (signal molecule)  Phosphorylation cascade  Transfer a phosphate from an ATP to a protein  Enzyme: protein kinase  Protein causes cellular response  Abnormal kinase activity can result in abnormal cell growth or cancer

Phosphorylation cascade

Inactivation  Protein phosphatases  Enzymes that remove phosphates  Turns off mechanism  Balance of the phosphorylation/dephosphoryl ation regulate activities of the cell

Second messengers  Non-protein, small, water-soluble molecules or ions  Diffuse quickly in the cytoplasm  Relay messages from the receptor to the target cells  G protein-coupled & tyrosine kinase pathways

Second messengers  Cyclic AMP (cAMP)  Cyclic adenosine monophophate  Calcium ions

cAMP pathway  Signal molecule attaches to the surface receptor.  Activates the G receptor  Activates the enzyme adenylyl cyclase to make cAMP.  cAMP then activates the target protein

cAMP pathway  Amplifies signal  Short-lived  Phosphodiesterases (enzyme)  Converts cAMP to AMP

cAMP pathway

Figure 11.11a ATPcAMP Adenylyl cyclase Pyrophosphate

Figure 11.11b cAMP AMP H2OH2O Phosphodiesterase

Cholera  Bacteria  Causes diarrhea  Toxin  Blocks the inhibitory enzyme  G-protein remains active-  Stimulates adenylyl cyclase  Makes excessive amounts of cAMP  Causes intestines to secrete ions (salts)

Nitrates  Smooth muscle relaxation  Dilation of blood vessels  Block the inhibitory enzyme  Prolongs cGMP  Continues affect

Calcium ions  Ca ion cytoplasmic levels usually low  Increased Ca levels can cause  Muscle contraction  Cell division  Hormone release

Calcium ions  Signal molecule attaches to the surface receptor  Activates the G receptor  Which activates the enzyme phospholipase C.  Which activates IP 3  Which causes the ER to release Ca ions  Ca ions cause affect

Response  Regulation of a cellular activity  Nucleus or cytoplasm  Protein synthesis  Activity of a protein

Response regulation  Amplification  Specificity  Scaffolding protein  Helps enhance response  Termination

Figure 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 Active protein kinase A (10 4 ) Inactive phosphorylase kinase Active phosphorylase kinase (10 5 ) Active glycogen phosphorylase (10 6 ) Inactive glycogen phosphorylase Glycogen Response Glucose 1-phosphate (10 8 molecules) Binding of epinephrine to G protein-coupled receptor (1 molecule)

Figure Signaling molecule Receptor Relay mole- cules Response 1 Response 2 Response 3 Response 4 Response 5 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

Apoptosis  Programmed cell death  Chop cells that are damaged  Protects surrounding cells  Embryonic cell growth

Fig µm

Apoptosis  Caspase  Enzymes that regulate cell death  Signal outside of cell  Nucleus can signal (DNA gone bad)  ER (Protein misfolding)

Apoptosis  Webbed feet or hands  Parkinson’s or Alzheimer’s  Cancer (melanoma)

Fig Interdigital tissue 1 mm