Receptors & Signaling

Assumed Knowledge

• Structure of membrane proteins• Ion concentrations across membranes• Second messengers in signal transduction• Regulation of protein activity through

phosphorylation

Membrane Proteins

• Mainly transmembrane• Act as receptors• Ligand binding causes a conformational

change – a change in the shape of the receptor

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

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

G proteins have three subunits – α (alpha), β (beta), and γ (gamma).

β and γ subunits are tightly bound together.

α binds to GDP

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 = cleavagePhosphorylation = addition of a phosphate group

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

Ion Concetrations

Ions – these are molecules with a charge + or –

Ion concentration – ions move down their concentrations gradient from [high] to [low]

[K+]160 mM

[K+]5 mM

[Na+]10 mM

[Na+]150 mM

[Cl-]5 mM

[Cl-]115 mM

[Ca2+]

0.2 M[Ca2+]2 mM

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Membrane potential = -70 mV

Anion –ve chargeCation +ve charge

[A-]40 mM

[A-]165 mM

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

Typically the interior is more negative

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 – repolarizationThere is a transient hyperpolarization where the membrane potential becomes more negative than normal

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

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

3. As Na+ enters the cell there is delayed opening of K+ channels

The membrane potential reaches +30mV where the Na+ channels close

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

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

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)

Second Messengers

Second messengers – these are molecules that relay signals from receptors on the cell surface to target molecules inside the cell

Examples include IP3, Ca2+, cAMP

Allows for amplification of the signal