3: Cell signalling

Question 1

Why cells need to communicate

Answer 1

Process information
Self preservation
Voluntary movement
Homeostasis

Question 2

Process of endocrine signalling

Answer 2

hormone travels within blood vessels to act on distant target cell

e.g glucagon stimulating glycogenesis and gluconeogenesis in liver

Question 3

Process of paracrine signalling

Answer 3

Hormone acts on an adjacent cell

e.g insulin inhibiting glucagon secretion

Question 4

Process of autocrine signalling

Answer 4

Signalling molecule acts on same cell

e.g growth factors stimulating mitogenesis

Question 5

Process of membrane attached protein signalling

Answer 5

Plasma membrane proteins on adjacent cells interacting

e.g HIV GP120 glycoprotein - CD4 receptors on T-lymphocytes

Question 6

4 types of cell signalling receptors

Answer 6

Ionotropic
G protein coupled
Enzyme - linked
Intracellular receptor

Question 7

Signal transduction events in Ionotropic receptors

Answer 7

1. Ligand binds to receptor protein
2. Change in conformation of channel protein –> opening of a pore
3. Pore allows ions to move in or out of cell according to respective concentration gradients

Question 8

Example of an Ionotropic receptor

Answer 8

Nicotinic Acetylcholine
Ligand: Acetylcholine ACh
Location: skeletal muscle
Physiological effect: Muscle contraction

Question 9

Signal transduction effects in G protein coupled receptors

Answer 9

1. 7-TM receptor and heterotrimeric G - protein(3 parts) are inactive
2. ligand binding changes conformation of receptor
3. Unassociated G-proteins bind to the receptor –> bound GDP molecule is phosphorylated to GTP, GDP exchanged
4. G-protein dissociated into two active components: alpha-subunit, beta,gamma subunit - they then bind to their target proteins
5. Internal GTPase activity on alpha subunit dephosphorylates GTP–>GDP
6. alpha-subunit dissociates from target protein –> inactive again
7. Receptor remains active as long as ligand is bound and can further activate heterotrimeric G-proteins

Question 10

Examples of G-protein coupled receptor

Answer 10

Adrenergic receptors are G coupled receptors (adrenaline)

Gs protein linked receptor (stimulatory) - stimulates adenylyl cyclase - converting ATP to cAMP, activates PKA- B1 receptor

Gi protein linked receptor (inhibitory) -
inhibits adenylyl cyclase - M2 receptor

Gq protein linked receptor
stimulates phospholipase C (PLC) - AT1A receptor - increase in Ca2+

Question 11

Signal transduction effects in Enzyme-linked receptors

Answer 11

1. ligand binding –> receptors clustering - dimerisation
2. receptor clustering activates enzyme activity within cytoplasm
3. enzymes phosphorylate receptor
4. Phosphorylation –>binding of signalling proteins to cytoplasmic domain
5. signalling proteins recruit other Sps –> signal generated within cell

Question 12

Examples of enzyme-linked receptors

Answer 12

Insulin receptor (CD220 antigen)
ligand: insulin
physiological effect: glucose uptake

ErbB receptors
ligand: Epidermal Growth Factor, Transforming Growth Factor
Physiological effect: cell growth, proliferation

Question 13

Signalling transduction effects in Type 1 Intracellular receptors

Answer 13

chaperone molecules (heart shock proteins=hsp)
1. Hormone binds to receptor –>hsp dissociates
2. 2 hormone bound receptors form a homodimer
3. Homodimer translocates to the nucleus –> binds to DNA

Question 14

Two types of Intracellular receptors

Answer 14

Type 1 - cytoplasmic
Type 2 - nuclear

Question 15

Signalling transduction effects in Type 2 intracellular receptors

Answer 15

1. Binding of hormone ligand –> transcriptional regulation

Question 16

Example of Type 1 Intracellular receptor

Answer 16

Type 1 - glucocorticoid receptor
ligands: cortisol, corticosterone
physiological effect: increased immune response, increased gluconeogenesis

Question 17

Example of Type 2 Intracellular receptor

Answer 17

Type 2- Thyroid hormone receptor
ligand: Thyroxine (T4), Triiodothyronine (T3)
Physiological effect: Growth and development

Question 18

What event happens after a ligand binds to a G-protein coupled receptor

Answer 18

GPCR shape change, unbound G-protein binds

Question 19

Direct effect of a-subunit of G protein following activation by GPCR

Answer 19

a- subunit dissociates from the (beta-gamma)subunit, interacts with target protein to propagate signal