Cellular Communication and Signaling Flashcards
What are microvilli?
Microvilli are tiny, hair-like projections on the surface of certain cells, primarily epithelial cells lining the intestines and other absorptive surfaces.
They are designed to increase the surface area of the cell, thereby enhancing its ability to absorb nutrients and other substances. Each microvillus contains a core of actin filaments that provide structural support.
What is the lipid bilayer permeable and impermeable to?
Permeable to: Non-polar, uncharged molecules
Impermeable to: Ions and large, charged molecules
Are the phospholipid byliayer choline heads polar or non polar?
Polar = hydrophilic = water loving
*Hydrophilic heads and hydrophobic tails.
Are the fatty acyl tails of the bilayer polar or non polar?
Nonpolar = hydrophobic = water hating = prevent water soluble solutes from passing though the middle of the bilayer.
Can ions and glucose cross the lipid bilayer?
No
Can O2, CO2 and steroid hormones cross the bilayer?
Yes
What percentage of the lipid bilayer is phospholipids?
75%
What percentage of the lipid bilayer is cholesterol?
20%
What makes up 5% of the lipid bilayer?
Glycolipids
What is the composition of the head of glycolipids?
Sugar (such as galactose)
What is the composition of the head of phospholipid?
Alcohol and phosphate
What is the composition of the head of cholesterol?
OH group
What does the cell membrane form?
A semi-permeable barrier
What makes up the cell membrane?
Lipid bilayer + membrane proteins
What are membrane proteins purpose?
Communication and exchange
What is on either side of a cell membrane?
Extracellular fluid/space
Cytosol
What principle is “Brownian motion” used to describe?
Everything is in constant motion - in the context of the cell membrane it is referring to the fact that the lipids in the bilayer and the membrane proteins are fluid/flexible.
It is important that the small molecules are flexible and dynamic for changing protein and lipid populations, cell growth, secretion and self-sealing
What side of the membrane are microvilli?
Apical
Where does epithelia sit?
ON an extracellular matrix structure called the basement membrane or basal lamina.
What joins the basal lamina to epithelial cells?
Hemidesmosomes
What does the basement membrane/basal lamina prevent?
Cell movement
What proteins are made in and secreted from epithelial cells?
Collagen and Laminin
What causes epidermolysis bullosa?
A collagen malfunction meaning that the basement membrane is no longer attached to skin epithelia
What is the predominant symptom resulting from epidermolysis bullosa?
Blistering
What are the three main functions of tight junctions?
Barrier - limiting the passage of ions and molecules between cells in the paracellular pathway
Gate - can allow certain solutes to flow through the paracellular pathway
Fence - prevent movement of proteins between apical and basolaterial domains
What forms the continuous structure of tight junctions around each epithelial cell?
Strands of Claudin - proteins linked to lipid bilayer of two cells pulling the bilayers very close together
What are the three main protein families of tight junctions?
JAMs (junctional adhesion molecules)
Claudins
Occludins
What is the name of the scaffolding proteins that connect tight junctions to the actin cytoskeleton?
Zona Occludin
Approximately how many types of Claudia proteins are there?
27
Which type of claudin protein is associated with transport?
Claudin 2
Where is Claudin 1 found?
Tight epithelia of the kidney and skin
Why is lack of Claudin 1 lethal?
Dehydration
What does Claudin 2 do?
Allows for transport of ions and water through tight junctions
What are examples of areas of the body where claudin 2 are?
Intestinal crypts and proximal renal tubule
What type of epithelia are claudin 2 found?
leaky epithelial
What is the structure of adheren junctions?
Belt structure = layers of actin proteins
Where are adheren junctions located?
Beneath tight junctions where two cells are in close contact
What does the formation of adherens junction initiate?
epithelia formation
What is E-cadherin?
Protein that makes up adheren junctions and directly connects cells.
What structure of adheren junctions enables some cell to cell signalling?
E-cadherins
What do desmosomal cadherins do?
Hold two cells together at a single spot
Are desmosomes continuous?
No
How do Cadherin and E-cadherins differ?
Cadherin holds cells together in a single spot, whereas E-cadherin is continuous.
What filament is embedded within hemidesmosomes plaque?
Keratin
What does plectin join keratin filaments to?
Integrins
What are gap junctions?
Tiny channels between cells
What are gap junctions made of?
Connexin proteins
How many connexin proteins are there in a single gap junction?
Six connexins = 1 connexon
2 connexons = 1 gap junction
Therefore, 12 connexins in a single gap junction
What is the key function of gap junctions?
Communication
What are the three main cytoskeletal types?
Actin Filaments
Intermediate filaments
Microtubules
What do actin filaments do?
Determine cell shape and drive movement of cells
What do intermediate filaments do?
Provide mechanical strength and resistance to shear stress with a diameter of 10nm.
What do microtubules do?
Position organelles, railroads for intracellular vesicle transport, form mitotic spindle, motile components of cilia
What is the diameter of microtubules?
25 nm
What is the diameter of actin filaments?
5-9 nm
What is the structure of actin filaments?
An actin filament is a 2 stranded helical polymers of actin.
Where do actin filaments assemble?
Adherens junctions
microvilli
What does cross-linking of proteins in actin filaments do?
Allows bundling to contribute to cell and microvilli shape
What is the structure of microtubules?
Long straight hollow cylinders made from alpha and beta tubulins
Are actin filaments or microtubules more rigid?
Microtubules
What are microtubules needed for?
Cell motility, cell division, and vesicle movement
What is kinesis and dynein and what do they do?
Molecular motors that allow transport of vesicles and organelles around the cell using ATP - in microtubules
What are the 4 types of cell to cell junctions?
Gap Junctions
Adhering junctions
Tight junctions
Desmosomes
What is the order that cellular signalling pathways occur?
Stimulus > Ligand > Receptor > Signal transduction > cellular response > negative feedback
What is the solubility of angiotensin 2?
Water soluble
*Therefor extracellular membrane receptor
Is the solubility of aldosterone?
Lipid Soluble
*Therefore instracelluar receptor
What is the solubility of ANP?
Water soluble
*Therefore extracellular membrane receptor
What is the solubility of ADH?
Water soluble
*Therefore extracellular membrane receptor
What type of receptors do water soluble ligands require?
Extracellular membrane receptors
Does aldosterone and ANP bind to G proteins?
No
What G proteins do Ang2 and ADH bind to?
Ang2 = Gaq
ADH = Gas
What is the second messenger of ANP?
cGMP (PKG)
What is the second messenger in the signal pathway of ADH?
cAMP (PKA)
What is the messanger pathway and effect of Ang2 binding to Gaq on membrane protein?
Ang2 –> Gaq –> PLC (Ca2+ and PCK) = increase in aldosterone
What is the aldosterone signalling pathway and its effect?
Aldosterone binds to intrcellular receptor and causes an increase in SGK, ENaC and blood pressure
What is the effect of the ANP signalling pathway?
ANP binds to mmebrane receptor (not G) and actaivates cGMP (PKGF) which leads to a decreases Na/K ATPase and blood pressure
What is the ADH pathway and effect?
Minds to membrane GaS receptor –> cAMP (PKA) = increase in AQP 2 and BP
What do effectors do?
Promote an increase in secondary messengers leading to a cellular response
How is water removed from the renal system?
By osmosis
How is glucose, amino acids and most mineral salts removed from the renal system?
By diffusion / active transport
How is metabolic waste such as urea, creatinines, uric acid and excess water and mineral salts removed from renal system?
Peeing urine
What are the main hormones that regulate NaCl and water transport pathways in the kidney tubules?
Angiotensin 2
Aldosterone
ANP (artial natrurtic peptide)
ADH (antidiuretic hormone)
What does ADH (vasopressin) do?
Increases water reabsorption
What does angiotensin 2 signal transduction in the adrenal cortex stimulate?
aldosterone release
What is triggger to be released from in kidney when there is low BP?
Renin
What does renin do?
Use the breakdown of angiotensinogen from the liver to form angiotensin 1 which is further cleaved by ACE to form angiotensin 2
Therefore renin is used in the production of Ang2 which is needed for aldosterone release.
What receptor does angiotensin 2 bind to?
AT1 GPCR
Where is AT1 GPCR located that angiotensin 2 binds to?
Zona glomerulsa cells of the adrenal cortex
Once Ang 2 bind to the AT1 receptor what is activated?
Gaq pathway
What is ACE?
Angiotensin coverting enzyme
What activates PIP2?
PLC
What are the two pathways activated by the activation of PIP2 in the Gq pathway?
INSP3 > Ca2+
DAG > PKC
What does aldosterone do to Na+?
Increase Na+ uptake from kidney tubules and increases blood pressure
What receptor does aldosterone bind to?
Mineralocorticoid receptor (MR)
What does the MR activate?
SGK gene (serum and glucocorticoid regulated kinase)
What is the primary response gene in signal transduction of aldosterone in epithelia?
SGK
What are the two effects of SGK?
1) decreases ENaC endocytosis and degradation
2) promotes transcription of secondary response genes e.g., ENaC
= both lead to increase Na+ transport, increase Na+ in ECF, water retention and this an increase in blood volume and blood pressure
Where is aldosterone released from?
Adrenal gland
Where are MR’s located?
Inside the nucleus of principal cells of the cortical collecting duct
How is angiotensin 2 signal transduction switched off?
BP goes back to normal - negative feedback kicks in - AT1 endocytose moves inside cell - GTPase, Ca2+ pump switches off signalling pathway and aldosterone levels decrease
What is ANP released in response to?
High BP
What is the ANP receptor?
An enzyme-linked receptor
What does an ANP receptor contain?
guanylyl cyclase enzymatic domains
What does ANP covert GTP into?
cGMP
What does cGMP activate and the further cascade?
PKG which then phosphorylates Na/K ATP-ase in the kidney cells which decreases it activity
Where is ANP released from?
Atria of there heart
What does an increase in ECF/BP lead to that triggers the ANP signal transduction pathway?
Leads to atrial stretch of the heart which triggers the released of ANP from the atria of the heart
Where is the ANP receptor located?
on the basolaterial membrane of collecting duct epithelial cells
What effect does Na/K ATPase phosphorylation have on Na+ transport?
Decrease therefore BP decreases
How does ADH mitigate dehydration?
Increase water reabsorption through aquaporin 2 in distal kidney (increases number of aquaporins and exocytosed to apical cell surface)
How is the ADH pathway switched off?
ECF osmolarity back to normal - ADH release from posterior pituitary stopped - V1 receptor endocytose - no cAMP increase, PKA inactive, AQP2 not phosphorylated = less water reabsorption
What do GI tract hormones and nerve signals promote?
Secretion of fluids and enzymes from epithelia and associated organs for the digestion of food
What are crypts?
Crypts are a pocket of epithelial cells in the lining of the stomach. Within crypts are different cell types that secrete range of substances that help protect the stomach lining from the acidic environment of the stomach.
What are the five cell types in the stomach?
Mucus cell
Parietal cell*
Enterrochromaffin-like cell (ECL)*
G-cell
D-cell
What are the two key ligands that bind to stomach parietal cells?
Histamine and ACh
What do stomach parietal cells secrete?
Hydrochloric acid (HCL) and intrinsic factor
What cells is histamine released from?
ECL
What stimulates the release of Histamine from ECL cells in the stomach?
Vagal nerve stimulating the enteric nerve which stimulates ECL cells
= histamine released from ECL cell
= histamine then acts on parietal cells
What method of cell-cell signalling is used between histamine and parietal cells?
Paracrine signalling (communication between two close cells).
What nerve connects the stomach and the brain?
Vagal nerve
What receptor does histamine bind to?
H2 receptor (GPCR coupled to Gas)
What occurs after histamine binds to H2 receptor?
Adenylate cyclase catalyses the conversion of ATP and cAMP activating protein kinase A (PKA)
PKA phosphorylates the H+/K+ pump prompting its exocytosis to the apical membrane
H+ is pumped out of the cell, as well as Cl- through CFTR to cause an increase in HCL in the stomach lumen.
How does Cl- exit stomach parietal cells?
Through CFTR channel
Where is the H2 receptor located?
Basolateral membrane of parietal epithelial cell
What does ACh bind to in stomach parietal cells?
M3 receptor (GPCR, Gaq)
Is Histamine or ACh associated with Q Gprotein?
ACh
ACh binds to M3 GPCR which involves Gaq protein. Whereas, Histamine binds to M2 GPCR with involved Gas protein.
What does Gaq activate?
PLC
Does ACh or Histamine activate PKA?
Histamine
ACh actiavtes PLC.
What does PLC do?
Breaks down PIP2 into IP3 and DAG
IP3 then binds to its receptor in the ER, Ca2+ pumped out of the ER
H+/K+ pump exocytosed to apical membrane
What does DAG activate?
PKC
Where is the Ip3 receptor located?
ER
Where is ACh released from?
Enteric nerves (which are stimulated by the vagal nerve)
What do protein pump inhibitors bind to?
H+/K+-ATPase
What are protein pump inhibitors used for in the stomach?
Used to treat acid reflux
What is helicobacter pylori?
Bacteria in the class of campylobacter.
What does H. Pylori do?
Disrupts the protective mucus layer sitting over the epithelial cells making them vulnerable to damage by acid.
Also seems to prevent inhibition of acid secretion.
In some people H. Pylori promotes gastric ulcers and gastric cancer.
What are the two pathways for pancreatic secretion?
(1) Acinar cells
(2) Duct cells
What do pancreatic acinar cells secrete?
Digestive enzymes
What is the major stimulus of acinar cells to secrete digestive enzymes?
CCK (cholecytoskinin)
What do pancreatic duct cells secrete?
Bicarbonate-rich fluid
What stimulates duct cells release of bicarbonate-rich fluid?
Secretin
Where does the pancreas secrete into?
The duodenum of the small intestine
What cells release CCK?
I cells in small intestine
What triggers the release of CCK from I cells?
The presence of food components such as amino acids and fatty acids
What cells does CCK act on?
Acinar cells
What does CCK stimulate exocytosis of?
CCK stimulates exocytosis of digestive enzymes - specially of zymogen granules which contain enzymes
What does CCK bind to?
CCK1 receptors (GPCR) on pancreatic acinar cells
What does CCK binding to CCK1 activate?
PLC
In the CCK signalling pathway what does IP3 cause the release of?
Ca2+ from the ER
What cells detect pH in duodenum?
Intestinal S cells
What cells secrete secretin?
S cells
What cells does secretin act on?
acinar duct cells
When secretin binds to its GPCR what does it activate?
AC (adenylate cyclase)
What is the effect of activating AC?
Breaks down ATP to cAMp activating PKA - PKA phosphorylates CFTR - activating CFTR at the apical membrane of pancreatic ductal cells and stimulating the secretion of HCO3 which neutralises pH. Osmotic gradient induces fluid secretion and helps move digestive enzymes into small intestine.
What does HCO3- do?
Neutralises pH
When CFTR of the apical membrane of pancreatic ductal cells is activated what is secreted?
HCO3-
How is bicarbonate-rich fluid affected in patients with CF?
It is absent or reduced because the CFTR is absent or dysfunctional therefore the pancreatic duct cells secretes no or limited amounts of bicarbonate-rich fluid into the lumen of the duct.
Patients with CF have a reduction of or no bicarbonate-fluid due to disfunctional CFTR - what is the effect of this?
1) Less alkalisation (therefore stomach remains acidic)
2) can’t move/flush enzymes into small intestine
What is the Gq protein pathway?
Gq = activates PLC which breaks down PIP2 into Ip3 and DAG
DAG activates PKC
IP3 binds to its receptor in ER (generally leading to Ca2+ being pumped out of the ER)
What is the Gs protein pathway?
Gs = activates AC which breaks down ATP into cAMP
cAMP activates PKA which phosphorylates a lot of things.
What G protein does CCK GPCR have?
Gq
What are the 4 ligands for cell signalling pathways in the kidney?
Ang 2
Aldosterone
ANP
ADH
What are the 4 ligands for cell signalling pathways in the GI tract?
Histamine
ACh
CCK
Secretin
If something is water soluble where is its receptor and what kidney ligands are water soluble?
Membrane bound receptor.
Ang2, ANP and ADH are water soluble therefore they have membrane bound receptors (aldosterone is a lipid soluble steroid hormone so its receptor is intracellular).
