Lipids in Cell Membranes Flashcards
What are some of the roles of phospholipids in the cell ?
- Make up lipid bilayer
- Participate in cell-cell communication mechanisms by giving rise to intracellular second messengers.
- serve as precursors for compounds that are released from cells and act on other cell types
What are phospholipids precursors of ?
Eicosanoids (inflammatory mediators)
What are the 6 steps of cell-to-cell communication ?
1) Synthesis of signal
2) Release of the signaling molecule by the signaling cell: exocytosis, diffusion, cell-cell contact
3) Transport of the signal to the target cell
4) Detection of the signal by a specific receptor protein
5) Change in cellular metabolism, function or development triggered by the receptor-signal complex
6) Removal of the signal or desensitisation
Do signals act at short or long range ?
Both
In animals, signaling by extracellular molecules can be classified into different types, what are these types ? Give that an example for each.
LONG RANGE
1) Endocrine (Hormones): released by endocrine gland and carried in bloodstream to distal target cells
E.g. Follicle-stimulating hormone released from the pituitary acts upon the ovary
2) Neurotransmission: transmission of nerve impulses across a synapse (between an axon and dendrite or between an axon and muscle cell) through a neurotransmitter
E.g. Breathing – the phrenic and thoracic nerves send impulses from the brain to the diaphragm
SHORT RANGE
1) Paracrine: signaling molecules only affect target cells in close proximity to secreting cells
E.g. Somatostatin release by pancreas cells acts locally. Neurotransmission can also be considered to be a type of paracrine signaling.
2) Autocrine: cells respond to substances that they themselves release
E.g. Some neurotransmitters and growth factors bind to the cells that release them.
3) Signalling by plasma membrane-attached proteins: Membrane-bound proteins can interact to signal
E.g. signalling by T cells in the immune system
Give an example of a mechanism which utilises many of the aforementioned cell signalling methods simultaneously.
Insulin is released from pancreatic β-cells acts in an autocrine (acts on β-cells), a paracrine (acts on alpha cells) and an endocrine (acts on liver/muscle/adipose tissue) manner.
Do signalling molecules enter cells ?
Many do not but lipid soluble signalling molecules (hydrophobic) do
How do signalling molecules which do not enter cells work ?
They act on extracellular membrane-bound receptors that control the production of intracellular chemicals (second messengers).
Where do the signalling molecules which do enter cells bind ?
Bind intracellular receptors
Give a few examples of types of intracellular and extracellular receptors, along with their time scale and a few examples of specific ones.
EXTRACELLULAR
-Ligand gated ion channels (ionotropic): Milliseconds.
E.g. Nicotinic ACh receptor
-G-protein coupled receptors (metabotropic): Seconds.
E.g. Muscarinic ACh receptor
-Kinase-linked receptors: Hours
E.g. Cytokine receptors
INTRACELLULAR
-Nuclear receptors: Hours.
E.g. Oestrogen receptor
Why do the receptors which take hours do so ?
Because they require transcription and gene synthesis
What are the two main paths taken inside the cell when extracellular signalling molecules bind to the receptor, to alter cell behaviour ?
FAST (seconds to mins)
Signalling molecule binds to receptor –> Altered Protein Function –> Altered Cytoplasmic Machinery –> Altered Cell Behaviour
SLOW (mins to hrs)
Signalling molecule binds to receptor –> Altered Protein Synthesis (through nucleus, requires transcription to take place) –> Altered Cytoplasmic Machinery –> Altered Cell Behaviour
Give examples of lipid-soluble molecules. Since they are hydrophobic, how do they remain in the plasma before entering the cell ?
Steroid hormones (cortisol, testosterone) Carried in plasma using a plasma protein
Is the intracellular receptor always in the nucleus ?
No
Describe the way in which cortisol alters cell function.
1) Carried in blood by plasma protein
2) Penetrates into the cell
3) Binds to intracellular receptor in cytosol
4) Activated receptor-cortisol complex moves into nucleus
5) Activated receptor-cortisol complex binds to regulatory region of target gene and activates transcription
What are the main molecules involved in Inositol phospholipid signalling pathway ? Where is the receptor found ?
Phosphatidylinositol 4,5-bisphosphate (PIP2), phospholipid receptor in lipid bilayer
Enzyme phospholipase C (PLC) (PIPI2 is its substrate)
What is the effect of PLC on PIP2 ?
PLC liberates two signalling molecules from PIP2; inositol 1,4,5 trisphosphate (IP3) and diacyglycerol (DAG)
Describe the Inositol phospholipid signalling pathway.
G-Protein linked receptor receives signal molecules –> G protein alpha subunit is activated –> Active protein switches on enzyme which cleaves IP3 from DAG –> IP3 binds to ER Calcium channels –> Ca2+ channels open and Calcium concentrations in cytosol increase –> Binding of DAG and Calcium to Protein Kinase C (enzyme) activates it –> PKC phosphorylates proteins and hence modifies their functions
Other than PKC, state an example where Calcium binds to proteins to regulate their function.
Ca2+/Calmodulin - activates proteins/enzymes through direct interaction
(e.g. myosin light chain kinase, which regulates smooth muscle contraction)
