Signalling 1 Flashcards
List the 3 major cell pathways, outlining the difference between them.
- Ion Channel Receptors (Ionotropic); Respond rapidly to stimuli, ligand-gated channels which allows an influx of particular ions to modify voltage potential in a neuron to either stimulate or inhibit it.
- G-protein coupled Receptors (Metabotropic); indirect gating, low and are seven-pass transmembrane receptors, with one end sitting outside the cell to bind to the ligand.
- Enzyme-linked; slow, respond to extracellular signals to regulate growth proliferation etc via intracellular transduction mechanisms which also often result in gene expression.
Brief notes on ionotrophic receptors and briefly outline what happens after a transmitter or ligand binds to it.
Ionotropic receptors, found on neurones, are made up of 4/5 protein subunits(ligand typically binds to the alpha subunit), each of which contributes to the pore of the ion channel. This receptor has 2 main domains extracellular(binds neurotransmitter) and membrane-spanning proteins(ion channel). - (DRAW THE PORE)
When a transmitter or ligand binds to the extracellular domain, an allosteric change occurs in which the charge alters of the pore which thus alters structure and function— the ion channel opens. Will then either simulate or inhibit an action potential.
Explain the 3 main ionotropic receptors and how they respond with glutamate.
Glutamate is the most common excitatory neurotransmitter in the brain which is accepted by at least 3 main classes of ionotropic receptors (AMPA, NMDA, KA). Each class consist of specific combination of receptor subunits(e.g. Heteromeric combination of 1 principle subunit and ant of the 4 modularly subunits).
Glutamate + AMPA or KA - Allows sodium in = Response is fast depolarization.
Glutamate + NMDA - Doesn’t allow as much sodium in and calcium = slow depolarization and 2nd messenger activation(calcium)
Show your understanding to the time frames involved n intracellular mechanisms. (Think about NMDA etc…)
How does disruption to these pathways lead to disease?
Some examples of disrupted cell signalling in disease include:Cancer cells have constant activation of signalling pathways instructing the cells to grow and divide. This often occurs because of changes (mutations) in receptors, protein kinases or transcription factors that keep the proteins an active state. Some examples of disrupted cell signalling in disease include:Cancer cells have constant activation of signalling pathways instructing the cells to grow and divide. This often occurs because of changes (mutations) in receptors, protein kinases or transcription factors that keep the proteins an active state.
Outline and illustrate the basic structure of g-protein coupled receptors.
Typically structure, 7 transmembrane spanning domains with a number of effector loops. the receptor itself hasn’t got inherent activity but is linked to an adaptor molecule(trimeric g-protein) which links receptor and adapts the response to an effector. (DRAW IT)
Give some examples of what g-protein receptors bind to.
Glutamate, GABA, Dopamine, Opioids, etc
Outline the overview of the g-protein mechanism with an illustration.
Receptor isn’t inherently active but is bound to an adapter molecule(trimeric g-protein).
First, the ligand or transmitter(e.g. GABA) will bind to the receptor. As a result, a GTP molecules will load onto the a-subunit present in the trimeric g-protein, which activates trimeric g-protein eliciting conformational change, then GTP converts into GTD. This links into an effector, which stimulates the production of a 2nd messenger which then activates a specific signaling cascade(there are 3 effector pathways).
Explain the GTPase function/mechanism.
Explain the structure and function of trimeric G-proteins.
The trimeric g-proteins are a large family of proteins. They couple receptors to effectors which catalyze formation of second messengers, or couple receptors directly to ion channels.
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Define the 6 types of g-alpha subunits and what they do.
Gsa - targets adenyle cyles switching it on
Gia - targets adenyle cyles switching it off
Gqa - targets phospholipase pathway switching it on
G0a - targets phospholipase pathway switching it off
Gta - shuts or open ion channles
Briefly outline + draw the trimeric g-protein sequence of events.
Outline/notes on the 3 g-protein effector pathways. (Give examples of applicable, draw if applicable)
Direct effector pathway(fast); This pathway has the alpha subunit link into the channels or pores to open or close causing a rapid response. (For example, )
Adenylyl cyclase pathway (medium-long);
PLC pathway (medium-long);
