Lecture 8. Cell to Cell Communication Flashcards
What are the two categories of cell signaling ?
- Contact dependent/Juxtacrine signaling
2. Secreted molecules
What are the types of juxtacrine signaling ?
- Gap junctions
- Plasmodesmata
- Notch
What are the types of secreted molecule signaling ?
- Autocrine signaling
- Paracrine signaling
- Endocrine signaling
- Paracrine signaling synaptic
What is juxtacrine signaling ?
The direct connection of adjacent cells by tiny channels that allow the movement of intracellular signaling molecules between cells
What do gap junctions provide ?
Cytoplasmic channels from one cell to an adjacent cell
What do gap junctions consist of ?
Membrane proteins called transmembrane connexins extending from the membrane of two cells
In gap junctions, what do the transmembrane connexins create ?
Pores
What are gap junctions necessary for ?
Communication between cells in many tissues such as heart muscle and in animal embryo
What are cardiomyocytes ?
Heart muscles which contract to make the heart beat
What is the lifecycle of a cardiomyocyte ?
They pump blood around the body from the moment of development of the heart in the womb until the moment of death
What is a characteristic of cardiomyocytes ?
They are autorhythmic
What is meant by autorhythmic ?
They generate their own action potential and rather than having a resting membrane potential they have a constantly cycling, changing membrane potential
What are the connections between cardiomyocytes called ?
Intercalated discs
What do intercalated discs contain ?
Anchoring proteins called desmosomes and the gap junctions
What do gap junctions form in cardiomyocytes ?
Channels between adjacent cardiac muscle fibres that allow the depolarising current produced by cations to flow from one cardiac muscle to the next
What are the gap junctions connecting the cardiomyocytes known as ?
Electrical coupling
What does electrical coupling in cardiac muscles allow ?
The quick transmission of action potentials and the coordinated contraction of the entire heart
What is the functional unit of contraction ?
Functional syncytium
What are plasmodesmata ?
Gaps that connect plant cells
What is inside the plasmodesmata ?
- A tubule of endoplasmic reticulum
2. Cytoplasmic sleece
What are the two ways that molecules can move through the plasmodesmata ?
- Proteins can move through the endoplasmic reticulum
2. Most things pass through the cytoplasmic sleeve
Why can most molecules pass through the cytoplasmic sleeve in the plasmodesmata ?
The cytoplasm is effectively continuous in between one cell and the next
Why is the effectively continuous cytoplasm important in plants ?
Allows metabolites, protein and nucleic acid to move between cells rapidly
What is the negative side of the continuous cytoplasmic sleeve ?
Viruses can spread rapidly through the plant
Why is notch signaling important ?
It is important in a number in developmental decisions, learning, memory and glial support of neurons
What is notch ?
A receptor molecule
Where is notch expressed ?
On the cell surface
What does notch interact with ?
Ligands on the cell surface
What are the ligands that notch interacts with in humans called ?
- Delta
2. Jagged
What are delta and jagged ?
Transmembrane proteins which have extracellular portions largely made up of EGF domains that allow interactions
What happens when delta binds to notch ?
An extracellular protease called ADAM10 carries out an S2 cleavage of notch by removing the extracellular domain to form an S3 protein
How is a notch intracellular domain formed from aa S3 protein ?
Gamma secretase within the membrane cleaves the membrane traversing part of the S3 protein
Where does the notch intracellular domain translocate to ?
The nucleus
What happens when the notch intracellular domain in the nucleus ?
It binds and removes the co-repressor allowing the transcription of target genes
What is autocrine signaling ?
When signaling molecules are released and then act on the cell that produces them
What are antigen presenting cells ?
Usually dendritic cells, which are phagocytic and can produce very small protein sequences called epitopes
What are epitopes ?
Very small protein sequences produces by antigen presenting cells
Where are epitopes presented on ?
The outside of the cell by a complex of proteins called a major histo-compatability complex
What does the MHC class II complex produce ?
A small amount of bacterial protein which is recognised by naiive T-cells using their receptor
What does the T-cell trigger the release of ?
Interleukin-2
What is interleukin-2 important for ?
The replication of T-cells so that the antigen can be recognised all over the body
How does the interleukin-2 act ?
On T-cells themselves by binding the proliferation of the T-cell clone - autocrine
What is paracrine signaling ?
Signaling molecules are released and act locally on nearby cells
What are some examples of paracrine signaling ?
- Cytokines released by immune cells act on multiple populations
- Morphogens released to drive patterning during development
- Neurotransmitters released locally act on multiple targets
What are morphogens ?
Signaling molecules that emanate from a restricted region of tissue and spread away from their source to form a gradient
How do Wnt proteins act ?
Wnt proteins act as morphogens in a concentration dependent manner through the formation of gradients within tissues
Where are WNTs produced ?
In the endoplasmic reticulum
What do WNTs undergo post translational modifications by ?
Palmitoleic and palmitic acid
Where do WNTs undergo post translational modifications ?
Conserved cysteine residues using the enzyme acyltransferase porcupine in the endoplasmic reticulum
What happens to WNTs at the endoplasmic reticulum ?
Vesicles bud off
What is feature of the golgi allows the vesicles to bind to the membrane with the aid of a chaperone protein ?
Its hydrophobic
What is the chaperone protein that aids vesicles to bind to the membrane ?
WNTless
Where does WNT signaling pathway occur at ?
Receptor cells
What is WNT protein’s receptor called ?
Frizzled
What does frizzled stimulate ?
The canonical pathway
What happens in the canonical pathway ?
A protein called beta catenin is stabilised in the cytoplasm
What happens to beta catenin when WNT signaling is not occuring ?
It gets degraded in the cytoplasm and cant carry out signaling function
What happens when there is a high concentration of beta catenin accumulating in the cytoplasm ?
It is able to be transported to the nucleus and can bind to the transcription factor TCF, which turns on new gene expression
What is an example of paracrine signaling ?
Neurotransmission
What is the neuromuscular junction ?
The place where neurons synapse directly onto a muscle
Where are neurotransmitters contained ?
Inside neurotransmitter vesicles
When does endocrine signaling occur ?
When a secretory cell secretes a signaling molecule/hormone into the blood stream for action at distal sites
Where is insulin released from ?
Pancreas
What is an example of endocrine signaling ?
Insulin
What does insulin promote ?
The uptake of glucose from the blood into organs
What is glucose stored in blood as ?
An energy containing molecule
What is transcribed to make insulin messenger RNA
Insulin gene
Where is insulin messenger RNA translated in ?
The endoplasmic reticulum
What is the insulin messenger RNA translated as ?
A preproinsulin
What is a preproinsulin ?
A much longer protein which is partially degraded to produce a mature molecules which is folded and released
Where is the preproinsulin transported to ?
The golgi
What happens to the preproinsulin in the golgi ?
Post translational modifications in the trans golgi network before being packaged into vesicles
What is the function of the secretory granules containing mature insulin >
Can travel within the cell and further signaling events occur to hone it to membrane
What is glucose sensed by ?
Glucose transporter on the cell surface
What happens when glucose is high ?
Insulin is stimulated to be released
Where is the glucose then transported to when glucose is high ?
Transported to the cytoplasm of the beta cells in the pancreas by glucose transporter
What can happen as a result of glucose being an energy substrate ?
It can be rapidly glycolysed and then pyruvate from the glycolysis is further metabolised in the TCA cycle in mitochondria, increasing ATP
What happens as a result of the elevated ATP levels ?
Drives the potassium channel, which changes the voltage in the cell and can open the calcium channels allowing calcium to flow and cause the cell to undergo calcium dependent exocytosis
What is paracrine signaling synaptic ?
When the signaling cell transmits information in the form of changes in membrane potential along the length of the cell