Signaling

Question 1

Ligands and Receptors

Answer 1

• signaling requires activation of a receptor, usually through an interaction with another molecule, called a ligand
• ligands take many forms, receptors are proteins
• ligand-receptor interactions are non-covalent (reversible binding)
• ligand binding induces a change in receptor conformation or induces dimerization of the receptor protein

Question 2

Signaling through conformational change

Answer 2

• receptor is either cell-surface of intracellular
• binding changes the shape of the receptor and alters is function by changing enzyme activity or binding affinity for something else
• activated receptor may change the cell

Question 3

Signal Amplification

Answer 3

usually involves second messenger molecules.

• activate one receptor makes many second messengers to get a response
• response occurs faster than without amp
• some second messengers can diffuse through the cytoplasm

Question 4

Why don’t all cells respond the same way to an extracellular signal?

Answer 4

• signal concentrations are variable (hormones)
• the number of available receptors changes
• intracellular second messenger systems are different
• types of receptors expressed in different cells are different

Question 5

Controlling concentration of an extracellular signal

Answer 5

• LOOK AT PICTURES!*
• concentration is the balance between synthesis and degredation
• in most cases rate of removal is constant, and to change concentration you change rate of synthesis
• fast degradation= short half life= fast changes in concentration
• slow degradation= long half life= slow changes in concentration

Question 6

Changing number of receptors

Answer 6

• LOOK AT GRAPH!*
• increasing receptors increases sensitivity to ligands
• increasing affinity means you dont need as many receptors but have high binding rates at lower concentrations

Question 7

Cellular Adaptation

Answer 7

changing the response to a constant concentration of ligand

1. prolonged receptor activation may cause changes that desensitize receptors (reduce their response)
2. Endocytosis can remove receptors from surface
3. Second messengers can change the rate of transcription of the receptor gene, leading to changes in the number of receptors on the cell surface

Question 8

Different Responses of Cells

Answer 8

• Same ligand and receptor cause different secondary pathways and therefore different responses-heart cell and salivary gland cell
• Same ligand can bind to different receptors in different cell types

Question 9

Signal Integration

Answer 9

• each cell integrates information from many signals
• one signal can bind to different receptors in different cells
• two signaling molecules may act through the same second messenger so that a boost in concentration in one signal makes the cell more sensitive to the other one

ex of signals: survive, divide, differentiate. nothing =apoptosis

Question 10

Routes of Delivery

Answer 10

Endocrine, Paracrine, Neuronal, Contact-Dependent

Question 11

Endocrine

Answer 11

carried through the bloodstream- low concentration since its spread out so need highest affinity

Question 12

Paracrine

Answer 12

from one cell to another cell. distance is slightly smaller so concentration is slightly higher so intermediate affinity

Question 13

Neuronal

Answer 13

from neuron to neuron across a synapse. highest concentration and shortest distance to relatively low affinity

Question 14

Contact dependent

Answer 14

through adhesions and cell-cell and cell-matrix junctions

Question 15

Classes of signaling molecules

Answer 15

• small diffusible molecules (NO, CO)
• hydrophobic molecules (steriods and eiconsinoids [bind to two receptor types])
• hydrophilic molecules (peptides, aa derivatives- glutamate)
• sensory signals (taste, smell)

Question 16

NO in blood

Answer 16

AP causes nitric oxide to be released in endothelial cells, diffuses across membranes, binds to target proteins (phosphodiesterase) and relaxes smooth muscle.

small molecules have shorter half lives

Question 17

Steriods

Answer 17

Bind to nuclear receptors (pass thru cell membranes) and are carried by binding proteins in the blood. longer half lives.

Question 18

Eicosinoids

Answer 18

derived from phospholipids and include prostaglandins, prostacyclins, leukotrienes and thromboxanes. function in inflammatory responses and blood clotting.
lipid soluble but bind to surface receptors, have short half lives, and usually act as autocrine (secreted by cell and bind to same cell).

are inhibited by aspirin and other NSAIDs, vioxx, and cortisone

Question 19

Hydrophilic molecules

Answer 19

peptides, aa derivatives

bind to surface cell receptors and have short half lives.

Question 20

sensory signals

Answer 20

EM radiation, vibration chemicals (sound, smell, taste). sensory receptors are cell surface molecules. not part of cell-cell but do rely on receptors and intracellular response mechanisms

Question 21

Steroids and signal transduction

Answer 21

-bind to receptor (intracellular) and change conformation so DNA binding site on receptor is open so it can change transcription rate of a gene (via promoter sequence)

Question 22

Partner TF

Answer 22

May be a TF already on promoter region

-ligand binds to receptor and complex binds to TF on promoter to alter transcription rate

Question 23

Signaling by transmembrane surface receptors

Answer 23

• ion channel linked- signal binds and opens ion channel
• G-protein linked receptors- signal binds and activates G protein that activates enzyme
• enzyme linked- signal in dimer or single molecule- binds to enzyme and activates domain or enzyme

Question 24

Gated Channels

Answer 24

• voltage gated
• ligand gated (extra or intracellular)
• stress gated
• ex-nerve synapse. Ca comes in (voltage gated), activates exocytosis to release NT, which binds to another gate (NT gated) across synapse

Question 25

Summary of signaling

Answer 25

• signaling occurs through non-covalent binding of ligands to proteins, changing protein conformation
• cellular respinse depends on the receptors and second messenger systems expressed
• steroid hormones bind to intracellular receptors to modify gene expression
• most other signal molecules bind cell surface receptors, ultimately modifying enzyme activity or opening ion channels