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BSCI330 > Lecture 12: Cellular Communication > Flashcards

Lecture 12: Cellular Communication Flashcards

1
Q

Steps of Cell Communication

A
  • Reception
  • Transduction
  • Response
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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
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3
Q

Transduction

A
  • The nature of signaling pathways: types of molecules involved in relaying signals
  • Behavior of molecules involved in relaying signals
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4
Q

Response

A
  • Types of cellular responses: specific physiological examples
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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
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6
Q

Paracrine signaling

A
  • The secreted molecules act as local mediators, affecting only cells in the immediate environment of the signaling cell
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7
Q

Endocrine signaling

A
  • The secreted molecules act as local mediators, affecting only cells in the immediate environment of the signaling cell
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8
Q

Synaptic signaling

A
  • Travel via axons - long distance down a neuron
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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
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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
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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

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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
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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
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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
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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
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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

BSCI330 (12 decks)

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