WEEK 4 (Intercellular communication and signal transduction) Flashcards
What is intercellular communication divided into?
- Direct (Gap junctions, TNTs, linkup of surface markers)
- Indirect (extracellular chemical messengers)
What are the extracellular chemical messengers?
- Paracrines/Autocrines
- Neurotransmitters
- Hormones
- Neurohormones
What is the function of gap junctions?
They allow the free movement of ions between neurons
What is the difference between paracrine and autocrine signalling?
In paracrine signalling a cell targets a neighbouring cell and in autocrine signalling a cel targets itself
Where are neuromuscular junctions found?
Between presynaptic neurons and target muscles
What is signal transduction?
The process in which binding of an extracellular messenger to the cell receptor is translated into changes in biochemistry, cell biology and gene transcription that make it possible for the cell to respond to the information that was received
simpler definition: The process in which the extracellular signal is transduced or changed into a form necessary to modify intracellular activities to accomplish the desired outcome
What is the importance of the difference between lipid soluble neurotransmitters and lipid insoluble neurotransmitters?
Lipid insoluble neurotransmitters act on the receptors on the surface of the cell surface membrane whereas the lipid soluble neurotransmitters enter the postsynaptic cell and act on the receptors within
Which gated channels can be found on the cell surface membrane of the postsynaptic neuron?
Chemically gated channels/Ligand gated channels
What happens in gap junctions?
Ions and small molecules are directly exchanged between closely associated interacting cells without ever entering the extracellular fluid
What is the function of tunnelling nanotubes (TNTs)?
Intercellular bridges that serve as a route for selective, relatively long transfer from one cell to another of large cargo (e.g proteins and organelles)
What is the major difference between TNTs and gap junctions?
TNTs can transfer larger cargo considerably longer distances than gap junctions can
What is the mechanism behind the transient direct link up of surface markers?
Cells with specialised markers on the surface membrane allow them to directly link with certain cells that have compatible markers for transient interactions
(this is how cell-destroying immune cells specifically recognise and selectively destroy only undesirable cells)
What are the four types of extracellular chemical messengers or “signal molecules”?
Paracrines/autocrines
Neurotransmitters
Hormones
Neurohormones
To exert its effect, an extracellular chemical messenger must bind with the target cell receptors ____________ for it
Specific
What percentage of all genes in humans code for synthesis of these membrane receptors?
5%
The four types of extracellular chemical messengers differ in their ______________ and the _____________ to and means by which they get to their site of action
Source
Distance
Why are Paracrines restricted to short distances and why do they not gain entry to the blood?
Paracrines are distributed by simple diffusion within the interstitial fluid so their action is restricted to short distances
They do not gain entry to the blood in any significant quantity because they are rapidly inactivated by locally existing enzymes
What is an example of a Paracrine and what is its function?
Histamine
Released from a specific type of connective tissue cell during an inflammatory response within an invaded or injured tissue. Histamine dilates the blood vessels which increases blood flow to the tissue and brings additional blood-borne combat supplies into the affected area
Define “Hormones”
Long-range chemical messengers specifically secreted into the blood by endocrine glands in response to an appropriate signal
How are non-target cells not influenced by any blood-borne hormones that reach them?
Only target cells of a particular hormone have membrane receptors for binding with this hormone
What are neurohormones?
Hormones released into the blood by neurosecretory neurons
What is the difference between a neuron and a neurosecretory neuron?
Neurons directly innervate target cells and release a neurotransmitter into the synaptic cleft whereas neurosecretory neurons release neurohormones into the blood to distant target cells
What are the two types of signal transduction?
- Lipid-soluble extracellular chemical messengers
- Water-soluble extracellular chemical messengers
Describe the function of lipid-soluble extracellular chemical messengers
These chemical messengers dissolve in and pass through the lipid bilayer of the target cell’s plasma membrane and bind to receptors inside the target cell to initiate the desired intracellular response such as controlling the level of activity of the transcribed protein
What happens when lipid soluble extracellular chemical messengers bind to their receptors?
Binding causes change in gene activity either by turning on or suppressing transcription of specific genes
Describe the function of water-soluble extracellular chemical messengers
These chemical messengers bind to specific receptors on the outer surface of the plasma membrane which triggers a sequence of intracellular events that controls a particular cellular activity
What is the pathway used by lipid-soluble extracellular messengers that bind to intracellular receptors?
Function in nucleus to change specific gene activity
What are the pathways used by water-soluble extracellular messengers that bind to surface membrane receptors?
- Bind to open and close chemically gated receptor-channels
- Bind to and activate receptor-enzyme complexes
(Use TYROSINE KINASE PATHWAY where the receptor itself functions as an enzyme or use JAK/SAT PATHWAY where the receptor and attached enzymes function as a unit) - Bind to G-protein-coupled receptors (GPCRs) and activate second-messenger pathways
What are the three general responses of a water-soluble extracellular messenger binding to its receptor?
- binding to a chemically gated receptor-channel opens or closes the channel with the resultant ion movement leading to the cell’s response
- binding to a receptor-enzyme complex activates tyrosine kinase which phosphorylates designated proteins that lead to a cell’s response
- binding to a G-protein-coupled receptor activates a second-messenger pathway that carries out the cell’s response
What are ‘protein kinases’?
The name for any enzyme that transfers a phosphate group from ATP to a particular intracellular protein
Since phosphorylation of a single protein does not get the job done, protein kinases act in a chain of reactions called a ____________ to pass along the signal to the final designated proteins capable of carrying out the desired effect
Cascade
Describe the stages of the Tyrosine Kinase pathway
- Two extracellular messengers bind to two tyrosine kinase receptor-enzymes, which pair, activating receptor-enzyme’s protein kinase (tyrosine kinase) site that faces the cytoplasm
- Tyrosine kinase site self-phosphorylates receptor-enzyme’s tyrosines
- Inactive designated protein binds to phosphorylated receptor-enzyme, which phosphorylates protein, activating it
- Active designated protein brings about desired response
In the JAK/STAT pathway where does the tyrosine kinase activity take place?
In separate cytosolic enzymes called Janus family tyrosine kinases (JAKs)
Describe the JAK/STAT pathway
- The receptor and attached enzymes function as a unit and two JAKs are attached (one on each side) to the receptor in the cytoplasm
- Binding of an extracellular messenger to the receptor on the ECF side causes a conformational change in the receptor that activates the JAKs bound to the cytosolic side of the receptor
- Activated JAKs phosphorylate signal transducers and activators of transcription (STAT) within the cytosol
- Phosphorylated STAT moves to the nucleus and turns on transcription of selected genes resulting in the synthesis of new proteins that carry out the cellular response
What is an example of a hormone that uses the JAK/STAT pathway?
Prolactin
stimulates milk secretion in lactating mothers
Describe the G-protein-coupled receptor (GPCR) pathway
- Extracellular (first) messenger binds to the G-protein-coupled receptor which activates the G protein
- The G protein shuttles along the membrane to activate the effector protein
- Effector produces a second messenger
- Second messenger activates protein kinase; the protein kinase then activates a designated protein
- Active designated protein brings about desired cellular response
What is distinguishable about the G-protein-coupled receptor (GPCR)?
It snakes through the membrane and is attached to a G protein
How can extracellular messengers be removed when no longer needed?
- degraded by the liver and and excreted in urine
- removed by receptor-mediated endocytosis (both the receptor and extracellular messenger are internalised by the target cell)
What is the name of a group of enzymes that reverse the effects of JAK/STAT and second-messenger signal transduction pathways?
Protein-phosphatases
They remove phosphate groups from designated proteins. The continual removal of phosphate groups from designated proteins quickly shut off a signal transduction pathway if a signal molecule is no longer bound at the cell surface
What is the difference between kinases and phosphatases?
Kinases activate a signaling pathway by phosphorylating designated proteins whereas phosphatases inactivate the pathway by dephosphorylating these proteins
Paracrines are either _____________ or _______________
Cytokines
Eicosanoids
What are Cytokines?
A collection of protein signal molecules secreted by cells of the immune system and other cell types that largely act locally to regulate immune responses
What are Eicosanoids?
A group of lipid signal molecules derived from a fatty acid in the plasma membrane of most cell types that act locally to regulate diverse cellular processes throughout the body
What are the different functions of Cytokines?
- regulates numerous activities of the immune system (e.g mediating inflammation, enhancing the activity of antibody-producing cells and virus-fighting cells)
- influencing cell growth and cell differentiation
What are Cytosines important in development referred to specifically as?
Growth factors
Which pathways do Cytokines usually function in?
Immune cytokines employ the JAK/STAT pathways and growth factors use the tyrosine kinase pathway
What happens to Eicosanoids once they act?
- Rapidly inactivated by local enzymes before they gain access to the blood
- if circulatory system is reached, they are swiftly degraded through the lungs
What are Eicosanoids and how are they formed into their classes?
Eicosanoids are a group of lipid signal molecules that act locally as paracrines to regulate physiological processes. They are modified 20-carbon fatty acids derived from arachidonic acid (a 20-carbon polyunsaturated fatty acid).
Arachidonic acid is split from the plasma membrane by a membrane-bound enzyme “Phospholipase A” which is converted into either PROSTAGLANDINS, THROMBOXANES and LEUKOTRIENES depending on the enzyme.
Cyclooxygenase (COX) = Prostaglandins & Thromboxanes
Lipopxygenase (LOX) = Leukotrienes
