Lecture 12: Cellular Communication Flashcards
1
Q
Steps of Cell Communication
A
- Reception
- Transduction
- Response
2
Q
Reception
A
- Signal molecule binding to a receptor
- Can be hydrophobic or hydrophilic
- The nature of signaling molecules: the types of signals, how they reach their receptors, overall effects
- The nature of receptors: types of receptors and how they respond to their signals
3
Q
Transduction
A
- The nature of signaling pathways: types of molecules involved in relaying signals
- Behavior of molecules involved in relaying signals
4
Q
Response
A
- Types of cellular responses: specific physiological examples
5
Q
The nature of signaling molecules: reaching their targets
A
- Extracellular signal molecules can act over short or long distances
- In most cases, signal molecules are secreted, but they can also be cell-surface
- Cells can also send signals to other cells of the same type, as well as to themselves
6
Q
Paracrine signaling
A
- The secreted molecules act as local mediators, affecting only cells in the immediate environment of the signaling cell
7
Q
Endocrine signaling
A
- The secreted molecules act as local mediators, affecting only cells in the immediate environment of the signaling cell
8
Q
Synaptic signaling
A
- Travel via axons - long distance down a neuron
9
Q
Autocrine signaling
A
- A cell releases signal molecules that can bind back to its own receptors
- During embryonic development, once a cell has committed to a particular pathway of differentiation, it may begin to secrete signals to itself that reinforce this developmental decision
10
Q
Contact-dependent signaling
A
- Some signal molecules remain bound to the surface of the signaling cell and influence only cells that contact it
- Common in embryonic development and immune responses
- Also important for maintaining our tissues under normal circumstances
11
Q
The nature of signaling molecules: Overall action
A
1) Extra cellular signals can act slowly or rapidly to alter the function of a target cell
2) Each cell is programmed to respond to specific combinations of extracellular signal molecules
- >Specific signals can promote cell survival
3) Different cells can respond differently to the same extracellular signal molecule
4) The same signaling molecule can have different effects on a cell type, depending on its concentration
12
Q
Extra cellular signals can act slowly or rapidly to alter the function of a target cell
A
- If the end result of a signal is to change the structure of an existing protein in the cytoplasm, for example, it could change the function of metabolism
- This could be a rapid function example
- The signal could also end up reaching the nucleus and change gene expression, which leads to changes in protein synthesis and alter cell behavior
- This would take longer to accomplish than changes to an existing protein
13
Q
Each cell is programmed to respond to specific combinations of extracellular signal molecules
A
- Not every cell can respond to a signaling molecule
- A typical cell in a multicellular organism is exposed to hundreds of different signals in its environment
- These signals can act in many millions of combinations
- A cell may be programmed to respond to one combination of signals by growth/division or another combination of signals by differentiating
- Another combination could also have it performing another specialized function such as contraction or secretion
14
Q
Specific signals can promote cell survival
A
- Most of the cells in a complex animal are also programmed to depend on a specific combination of signals simply to survive
- When deprived of these signals (in a culture dish, for example) a cell activates a suicide program (apoptosis)
- Because different types of cells require different combinations of survival signals, each cell type is restricted to different environments in the body (lung cells need lung environment signals)
- This is how tissues maintain localization
15
Q
Different cells can respond differently to the same extracellular signal molecule
A
- Cellular responses vary according to:
- > Unique collection of receptor proteins the cell possesses
- > The intracellular signaling machinery by which the cell integrates and interprets what it receives, which determines the particular subset of signals a cell can respond to
- The same signal molecule often has different effects on different target cells
- > Ex: Acetylcholine - neurotransmitter
16
Q
The same signaling molecule can have different effects on a cell type, depending on its concentration
A
- Ex: Embryonic development
- Molecules can morphogens diffuse out from signaling centers in developing tissues, creating a morphogen concentration gradient
- Cells adopt different fates depending on their position in the gradient. In this way, layers of cells develop, each with a different function
- Cells react to the different concentrations of morphogens being released
17
Q
The nature of signaling molecules: Types of signals
A
- Cells are specialized to receive and respond to a wide variety of stimuli
- Mechanical stimuli:
- > Adhesion to substrates, membrane distortion, sound
- Light
- Heat
- Chemical —> come in a variety of forms
18
Q
Chemical stimuli
A
- Amino acids, small molecules, and proteins
- Nucleotides
- Steroids
- Fatty acid derivatives
- Even dissolved gases (nitric oxide and carbon monoxide)
- These signals are either hydrophobic or hydrophilic, which can affect how they travel from one cell to another and whether they can cross the plasma membrane
- Most of the signal molecules are secreted from the signaling cell into the extracellular space by exocytosis
- Others are:
- > Exposed to the extracellular since which remaining tightly bound to the signaling cell’s surface
- > Released by diffusion through the plasma membrane
- > This depends on their intrinsic nature
19
Q
Lipid soluble signals
A
- Many signaling molecules are lipid soluble and can simply diffuse across the plasma membrane
- Example: steroid hormones and gaseous signaling molecules (e.g. nitric oxide)
20
Q
Steroid hormones
A
- Vary in chemical structure, but all are synthesized from cholesterol
- Cortisol, sex hormones, Vitamin D
- Travel to their target cells via carrier proteins
- Bind to intracellular receptors, which can either by cytosolic or nuclear
- Once bound to the intracellular receptors, they sometimes move to the nucleus in order to serve as transcription factors
21
Q
Cortisol
A
- Adrenal glands
- Influences metabolism (stress hormone)
22
Q
Sex hormones
A
- ovaries and testes
- Determine secondary sex characteristics that distinguish males and females
23
Q
Vitamin D
A
- Skin in response to sunlight
- Regulates Ca+2 uptake/secretion
24
Q
Thyroxin
A
- Non-steroid, tyrosine derivative
- Thyroid glands
- Regulates metabolism
25
Q
The nature of receptors: intracellular receptors
A
- The receptors for steroid hormones are members of the nuclear receptor subfamily
- Prior to ligand binding, these receptors are bound to an inhibitory protein and are inactive
- Ligand binding causes a conformational change in the receptor, which causes an inhibitory protein to dissociate
- > Also releases a nuclear translocation signal
- > They translocate into the nucleus
- Exposes a site which binds to the promoter region upstream of a specific targeted gene
- Transcription of that gene is then increased, producing specific proteins —> changes in cell behavior
- > Transcription can also be decreased, decreasing the production of specific proteins
- > This is one of those slow modes of action that leads to long-lasting effects on cell behavior
26
Q
Hydrophilic/lipid insoluble signals
A
- The majority of chemical stimuli are small, polar, water soluble molecules, for example:
- > Most neurotransmitters
- > Peptide hormones
- > Growth factors
- > Most olfactants (things that you can smell)
- > Tastants (things that you can taste)
- These molecules cannot cross all membranes and so must bind to sites on cell surface receptors
27
Q
Cell-surface receptors
A
- 3 major types
- > Ligand-gated ion channels “ionotropic receptors”
- > Enzyme coupled receptors
- > G-protein-coupled receptors
28
Q
Ion channel coupled receptors
A
- Involved in synaptic signaling between neurons and other excitable cells (are also involved in other types of signaling)
- Intracellular signals can also lead to changes in ion channels
- Opened by ligand binding
- Are opened or closed by a small number of neurotransmitters
- Alter ion permeability —> membrane potential changes
29
Q
G-protein-coupled receptors
A
- Large family of multipass transmembrane proteins
- Have 7 transmembrane regions
- Indirectly regulate the activity of a nearby target protein (e.g. enzyme or channel) that is located in the membrane
- > Uses an intermediary called a G-protein (3 proteins that form a complex, one of which binds to GDP)
- > When the GDP is exchanged for GTP, the G-protein becomes active
- Contain a GTP binding protein complex that acts as the ‘middle man’ between an activated receptor and its target
30
Q
Enzyme-coupled receptors
A
- Single-pass transmembrane proteins of varies structure
- Either function directly as protein kinases or associate directly with and activate other protein kinases
- Indirectly regulate the activity of a nearby target protein (e.g. enzyme or channel) that is located in the membrane or cytosol - often via kinase “cascade”
31
Q
Intracellular signaling molecules and their behavior
A
- Cell-surface receptors carry the signal (1st messenger) across the plasma membrane
- A combination of activated enzymes and small intracellular molecules called second messengers amplify the signal and spread it throughout the cell
- Activated effector proteins regulate cell’s response
- For hydrophobic signals, there’s no need for second messengers; they directly activate an effector protein
32
Q
Molecular switches
A
- Many intracellular signaling proteins function as these that are activated by:
- > Kinases/phosphatases: phosphorylation/dephosphorylation
- > GTPases/GTP-binding proteins
33
Q
Signaling complexes
A
- Enzymes activated by a receptor protein (second messengers) often form protein complexes called ‘signaling complexes’, which regulate:
- > Speed, efficiency, specificity of a cellular response
-These complexes can be:
- Organized around a “scaffold” protein
- > As a result, the second messengers attached to the scaffold protein can interact with each other or a single kinase can phosphorylate all of them rapidly
- > This can allow a single receptor to have a rapid and complex response
- > Also allows us to integrate signals
- Assembled following receptor activation
- > Second messengers can bind directly to the receptor after it has been phosphorylated which forms this higher order complex
- > After the higher order complex has been formed, then come the downstream signals
- Assembled on phosphorylated phosphoinositide (polar head group is based off of inositol) lipids in the membrane
- > The membrane itself serves as the assembly point for a higher order complex that can then send downstream signals
34
Q
Receptor Tyrosine Kinase activation
A
- Dimerize and phosphorylate themselves upon ligand binding
- > A signal molecule acts as a dimer and brings 2 molecules of the receptor together
- > The tyrosine kinase domains then phosphorylate each other, which recruits second messengers to bind to the receptor
- Proteins specialized to bind phosphorylated tyrosines then bind (Have SH2 groups)
- > The SH2 groups have slightly different sequences which allows them to bind to the different phosphorylated tyrosines
- > The SH2 group proteins can then become activated by either binding or becoming phosphorylated
- One of these signaling proteins can be the lipase, phospholipase C (lipases hydrolize lipids)
- > Can also be activated by G-proteins
- > Cleaves PIP2, which creates IP3, which releases Ca from the ER, and diacylglycerol, which this and Ca binds to protein kinase C to activate it
- Another one of these signaling proteins could be the GTPase, Ras
- > Covalently attached lipid anchor: inner leaflet of plasma membrane
- > Ras then initiates a cascade of phosphorylation events mediated by a group of kinases (MAP kinases)
35
Q
The Role of Calcium as an Intracellular Messenger
A
- Ca2+ ions have a key role in a remarkable variety of cell activities:
- > muscle contraction,
- > cell division,
- > secretion (exocytosis),
- > endocytosis,
- > fertilization,
- > synaptic transmission,
- > metabolism,
- > cell movement
