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Receptors & Signaling. Assumed Knowledge Structure of membrane proteins Ion concentrations across membranes Second messengers in signal transduction Regulation.

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Presentation on theme: "Receptors & Signaling. Assumed Knowledge Structure of membrane proteins Ion concentrations across membranes Second messengers in signal transduction Regulation."— Presentation transcript:

1 Receptors & Signaling

2 Assumed Knowledge Structure of membrane proteins Ion concentrations across membranes Second messengers in signal transduction Regulation of protein activity through phosphorylation

3 Membrane Proteins Mainly transmembrane Act as receptors Ligand binding causes a conformational change – a change in the shape of the receptor

4 G Protein coupled receptors (GPCR) – these have a transmembrane bit with 7 helices spanning the membrane The extracellular part binds to the ligand The intracellular part binds to the G protein

5 G Protein – these are proteins that bind to the guanine nucleotide (GTP – guanosine triphosphate, GDP – guanosine diphosphate) Hydrolysis of GTP releases a phosphate group which can act on other molecules – transmits the signal GTP > GDP + P

6 G proteins have three subunits – α (alpha), β (beta), and γ (gamma). β and γ subunits are tightly bound together. α binds to GDP

7 Ligand binding to the transmembrane protein causes a conformational change and release of the α subunit The α subunit exchanges GDP > GTP and becomes active The α subunit meets a target and phosphorylates it (adds a phosphate group from GTP converting it to GDP – this is hydrolysis of GTP) Hydrolysis = cleavage Phosphorylation = addition of a phosphate group

8 Now the α subunit is bound to GDP, it becomes inactive again and re-associates with the transmembrane protein and the β and γ subunits

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10 Ion Concetrations Ions – these are molecules with a charge + or – Ion concentration – ions move down their concentrations gradient from [high] to [low]

11 [K + ] 160 mM [K + ] 5 mM [Na + ] 10 mM [Na + ] 150 mM [Cl - ] 5 mM [Cl - ] 115 mM [Ca 2+ ] 0.2  M [Ca 2+ ] 2 mM Membrane potential = -70 mV Anion –ve charge Cation +ve charge [A - ] 40 mM [A - ] 165 mM

12 Membrane Potential – this is the difference in charge between the interior and exterior of a cell Typically the interior is more negative

13 Action potentials – these are rapid rises and falls in the membrane potential. In neurons these act as nerve signals The interior becomes rapidly positive or less negative – depolarization. This is followed by a rapid return to a negative membrane potential – repolarization There is a transient hyperpolarization where the membrane potential becomes more negative than normal

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15 1.An stimulus is received by a nerve causing Na + channels to open – Na + moves into the cell. The membrane potential begins to become more positive

16 2.When the membrane potential reaches the threshold level (-55mV) there is an opening of more Na + channels allowing more Na + to enter the cell This is an ‘all-or-nothing’ moment meaning if the membrane potential doesn’t reach the threshold there will be no action potential but if it reaches the threshold there no turning back

17 3. As Na + enters the cell there is delayed opening of K + channels The membrane potential reaches +30mV where the Na + channels close

18 4. When the K + open, K + leaves the cell causing the membrane to start to become more negative again

19 5.When the K + channels finally close there is slightly more K + on the outside than Na + meaning the membrane potential dips below the normal resting potential (-70mV) Essentially more positive charges leave the cell than entered

20 5. There is a refractory period where the [K + ] and [Na + ] are returned to their original state Carried out by the Na + /K + -ATPase (a pump that uses ATP for energy)

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22 Second Messengers Second messengers – these are molecules that relay signals from receptors on the cell surface to target molecules inside the cell Examples include IP 3, Ca 2+, cAMP Allows for amplification of the signal


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