Cellular communication Flashcards
What are the 3 basic types of cell junctions?
Anchoring, Communicating, and Occluding
Name 2 types of communicating junctions used to transmit electrical signals from one axon to another.
- Chemical synapse
2. Gap junction
.Which protein subunits are involved in formation of gap junctions?
connexins/connexons
How many connexin subunits make up a gap junction?
6
What’s the difference between a gap junction and chemical synapse?
Unlike in chemical synapse, materials pass between cells WITHOUT INTERACTING WITH EXTRACELLULAR FLUID
What factors affect the diameter of gap junctions?
[Ca2+ ions]
pH
hormones
electrical potential
Define a chemical synapse.
The junction between a nerve fiber and non-neuronal cell (ex: muscle) or between 2 nerve fibers, where electrical signals are transmitted
What implications are incurred by mutations of connexin?
- formation of cataracts in the eyes
- deafness
- charcot-marie-tooth disease
What does DAG stand for?
Diacylglycerol
Name 5 second messsengers.
- IP3
- DAG
- Calcium 2+
- cAMP
- cGMP
How can chemical messengers be classified?
based on function and chemical structure
What are the functional classes of chemical messengers and give examples of each.
- Paracrines (ex: growth factors)
- Neurotransmitters (acetylcholine)
- Hormones (insulin)
What are the five chemical classes of chemical messengers? Give an example of each.
- Amino acids (glutamate)
- Amines (dopamine, epinephrine, norepinephrine)
- Proteins/Polypeptides
- Steroids (corticosteroid)
- Eicosanoids (prostaglandins, leukotrienes)
Which chemical messenger makes up a majority of all the chemical messengers?
Proteins/Peptidtes
Which chemical messengers cannot be stored in vesicles?
Steroids and Eicosanoids
What factors affect the magnitude of a target cell’s response?
- concentration of messenger
- number of receptors
- affinity of receptors to messengers
Where are receptors of lipophilic messengers usually located?
In the cytosol
In the nucleus
How do lipophilic messengers cause a response in the target cell?
Once inside the nucleus, they bind to HRE (hormone response element) regions before genes to affect synthesis of proteins
When two hormone receptors are bound to an HRE region, what is the process called?
Dimerization
Where are the receptors for lipophobic messengers located?
On the plasma membrane
Where does the letter G come from, for the G protein?
Its ability to bind guanosine nucleotides
What is the difference between fast ligand-gated and slow ligand-gated channels?
Fast ligand-gated channels; receptor and channel are the same protein, effects immediate and brief, ligands can only OPEN the channel, but not close it
Slow ligand-gated channels; receptor and channel are different proteins , effects slow and prolonged, ligands can OPEN and CLOSE the channel
G-protein linked receptors are what type of channel?
Slow channel-linked (ligand-gated) channel
3 ways Calcium is removed from the cytosol
- Active transport across plasma membrane
- Active transport into organelles
- Sequestering with proteins in cytosol
Location of the G-protein in the G-protein linked receptors.
It faces intracellular side of the plasma membrane
Function of G-proteins
Link RECEPTORS on plasma membrane to EFFECTORS (enzymes and ion channels) in the plasma membrane
G protein structure
3 subunits
-alpha, beta and gamma
Which G protein subunit binds to guanosine?
the alpha unit
How does G protein deactivate itself?
it is an enzyme, so soon after it binds GTP, it hydrolyzes GTP back to GDP and so deactivates itself
Functional classes of G-proteins
- Inhibitory/ Gi - inhibit amplifier enzymes
- Stimulatory / Gs - activate amplifier enzymes
- Affect ion channels
Structural classification of G-proteins
Monomeric - one small GTP
Trimeric - the 3 subunit GTP structure
How does Vibrio Cholerae affect G-protein action in cells to cause cholera?
The bacterium releases a toxin that binds to the G-protein coupled receptor, causing constant activation of G protein. G protein then overstimulates production of adenylate cyclase = excess cAMP –> constant activation of protein kinases that affect Chlorine channels (CFTR; cystic fibrosis transmembrane conductance regulator) causing excess chlorine to be pumped out = high intestinal concentration of chlorine and water to leave cell via osmosis to higher concentration leading to diarrhea
The two major categories of intercellular communication
Electrical/Synaptic
Hormonal/Chemical
The four types of chemical intercellular communication
*MNEMONIC: PAJE armstrong
Paracrine (same tissue)
Autocrine (cell communicates with itself)
Juxtacrine (between adjacent cells)
Endocrine (cells in another distant location)
3 stages of cell signalling
- reception
- transduction
- response
How much greater is the concentration of Calcium outside the cell than inside?
10,000x
The 3 proteins calcium binds to
- Troponin - for muscle contraction
- Calmodulin - smooth muscle contraction, apoptosis
- Calbindin - absorption of Calcium from intestines, promotes reabsorption of calcium for bone
In the JAK-STAT pathway. JAK stands for? STAT stands for?
JAK - JAnus Kinase
STAT - signal transducer and activator of transcription
True or false: STAT proteins activate JAK
FALSE; JAK activates STAT
In each STAT dimer, they bind to the __________ of the other STAT.
Phosphotyrosine
Explain the JAK-STAT pathway.
Ligand binds to JAK receptor
2 JAK receptors brought together to form a dimer
JAKs are close enough to activate each other
Receptors also get activated (phosphorylated in the process)
STAT binds and also gets activated and form a STAT dimer (active transcription factor) each binding to the other’s phosphotyrosine domain
STAT dimer enters nucleus and binds to specific DNA sequence at promoter region to activate gene transcription
How is the JAK-STAT pathway shut down?
dephosphorylation of other proteins involved in the pathway
Two hormones that bind to JAK receptors and their effects.
Leptin - regulation of body weight
Growth hormone - stimulate growth
3 paracrines/cytokines that bind to JAK-linked receptors and their effects
Interleukin 2 –> lympocyte proliferation during immune response
IFN-gamma/Type 2 IFN —> activation of macrophages
IFN-beta and alpha –> induce antiviral state
2 ways drugs targeting JAK-STAT pathway work.
- Blocking ligand receptors (Injection)
2. Inhibit kinase activity of JAK (Drug)
STUDY BREAK
Drugs targeting the JAK-STAT pathway are used to turn down the immune response.
ex: Tofacitinib (rheumatoid arthritis treatment) and Baxiliximab (prevent transplant rejection)
Presynaptic dense bodies
Also called active zones, the area where neurotransmitter release occurs
The protein that binds vesicles to actin, microtubule, and spectrin filaments.
Synapsin 1
Describe the mechanism of neurotransmitter release
- When voltage changes due to action potential transmission, Calcium voltage gated channels open
- Influx of calcium at active zone
- Calcium binds to calmodulin to form Calcium-calmodulin complex
- Calcium calmodulin complex activates CaM kinase 2 (calmodulin dependent protein kinase 2)
- CaM kinase 2 phosphorylates synapsin 1
- synapsin 1 relases the vesicle which is now free to go for exocytosis
Proteins involved in guiding free vesicles to active zones
Rab 3a and Rab 3b on the vesicle membrane
Which proteins are involved in vesicles binding to the plasma membrane for exocytosis?
Synaptobrevin on vesicle membrane binds to syntaxin on plasma membrane
3 examples of G-protein coupled receptors
- Beta adrenergic receptors in cardiac muscle bind epinephrine
- Rhodopsin receptors bind to retinal
- Prostaglandin E2 (PGE2) receptors bind prostaglandin
Classification of receptors
Plasma membrane receptors (on/in cell membrane); include 1. G-protein coupled 2. Enzyme-coupled 3. Ion channels
Intracellular receptors (are for hormones and other fat-soluble ligands); include 1. Nuclear receptors 2. Cystoplasmic receptors
