Communication between cells

Question 1

Why do cells communicate? (x4 – 2nd point has 2 points)

Answer 1

Process information – from sensory stimuli e.g. visual and sounds. Survival – Identify danger and take appropriate actions through SPINAL REFLEXES and SYMPATHETIC NERVOUS SYSTEM (fight or flight response). Voluntary movement – brain communicates with skeletal muscle. Homeostasis – thermoregulation, glucose…. Requires hormonal communication between cells.

Question 2

What is intercellular communication?

Answer 2

Communication BETWEEN cells.

Question 3

What is intracellular communication?

Answer 3

Communication WITHIN a cell.

Question 4

What are the types of intercellular signalling? (x4)

Answer 4

Endocrine Paracrine Autocrine Signalling between membrane attached proteins. (EXOCRINE IS NOT INTERCELLULAR because it involves secretion of a chemical and that chemical is functional extracellular and affects extracellular molecules like food.)

Question 5

What is endocrine signalling?

Answer 5

Hormone produced in one cell type and travelling within blood vessels to act on a distant target cell of a different cell type.

Question 6

Examples of endocrine communication? (x3)

Answer 6

Glucagon – increase blood glucose. Insulin – produced by beta cells and acts on liver, muscle and adipose. Adrenaline – produced in the adrenal glands on the trachea.

Question 7

Give a detailed example of endocrine communication. FLIP CARD FOR WHAT I HAVE TO EXPLAIN.

Answer 7

Hypoglycaemia Blood glucose is regulated by the pancreas. Islets of Langerhans – alpha and beta cells produce glucagon and insulin respectively. Glucagon increases blood glucose by stimulating glycogenolysis (most important process of the two) and gluconeogenesis in the LIVER.

Question 8

What does adrenaline do?

Answer 8

Example of endocrine communication. Prepares body for fight or flight. Increases heart rate, glucose, dilation of air pathways, vasodilation of arteries in muscles and brain.

Question 9

What is paracrine signalling?

Answer 9

Hormone acts on an adjacent and nearby cells.

Question 10

Examples of paracrine signalling?

Answer 10

Insulin and its effect on nearby alpha cells. Nitric oxide produced by endothelial cells in blood vessels and affects smooth muscle = vasodilation. Osteoclasts activating factors are produces by adjacent osteoclasts causing burn turnover.

Question 11

Give a detailed example of paracrine communication. FLIP CARD FOR WHAT I HAVE TO EXPLAIN.

Answer 11

Hyperglycaemia Beta cells produce insulin. Insulin acts on ADJACENT alpha cells (very close to it) to reduce levels of glucagon production. e.g. paracrine – still within Islets of Langerhans, but beta cell signalling to adjacent cell.

Question 12

What is signalling between membrane attached proteins?

Answer 12

Interaction between plasma membrane proteins (usually receptors) on adjacent cells. Two floating cells.

Question 13

Examples of membrane attached proteins communication? (x3)

Answer 13

Interaction between T-lymphocytes and MHC in Immunology. HIV GP120 glycoprotein interacting with T-lymphocytes receptors. Bacterial wall components interacting with toll-like receptors on haematopoietic cells.

Question 14

Give a detailed example of signalling between membrane attached proteins. FLIP CARD FOR WHAT I HAVE TO EXPLAIN.

Answer 14

Blood-borne virus. Hepaptitis C found in blood. Detected within bloodstream by APC. APC digests pathogen and expresses MHC class II molecules on its surface. APC now presents to a T-lymphocyte. T-cell receptor (TCR) on T-lymphocyte engages with MHC molecule through TCR interaction. This interaction is membrane-attached protein signalling.

Question 15

What is autocrine signalling?

Answer 15

Signalling molecule produced by a cell acts on the same cell.

Question 16

Examples of autocrine signalling? (x3) (x1 general point)

Answer 16

A LOT ARE RESPONSIBLE FOR NEGATIVE FEEDBACK SYSTEMS. T-lymphocyte produces interleukin-2. Acetylcholine acts on the same terminal as it was released in a synapse. Growth factors from tumour cells –> mitogenesis.

Question 17

Give a detailed example of autocrine signalling. FLIP CARD FOR WHAT I HAVE TO EXPLAIN.

Answer 17

Interleukin-2. TCR has been activated because of membrane attached protein signalling with MHC. Activated TCR will initiate cascade of reactions within T-cell. Expresses interleukin-2 (IL-2) receptor on surface. T-lymphocyte also secretes IL-2 which BINDS TO IL-2 RECEPTOR ON SAME CELL, and binds to IL-2 receptor on adjacent activated T-cell (paracrine signalling). The action of this molecule mediates the immune response – acts as part of both positive and negative feedback loops in mounting and dampening immune responses.

Question 18

What are the four different types of receptor – that allow for transmission of an extracellular signal into a cell?

Answer 18

Ionotropic receptor. G-protein coupled receptor. Enzyme-linked receptor. Intracellular receptor.

Question 19

NOTE

Answer 19

WHEN I RECALL EXAMPLES OF EACH RECEPTOR, EMPHASISE KNOWING THE RECEPTOR RATHER THAN THE MECHANISM AND PHYSIOLOGICAL EFFECT. ALTHOUGH KNOWING BOTH IS GOOD, I THINK THE IMPORTANT STUFF IS KNOWING NAMES.

Question 20

In biochemistry, what is a ligand?

Answer 20

A molecule that bind to another (usually larger) molecule.

Question 21

How does an Ionotropic receptor work?

Answer 21

1. Ligand binds to the receptor protein. 2. Results in change in conformation of channel protein which opens the pore. 3. Pore allows ions to move in or out of the cell according to their respective concentration gradient. Remember, these are ion channels not activated by voltage, but by a ligand.

Question 22

Examples of ionotropic receptors? (x2) Recall ligand, location and physiological effect.

Answer 22

Nicotinic Acetylcholine LIGAND: Acetylcholine LOCATION: neuromuscular junction, but found on the skeletal muscle PHYSIOLOGICAL EFFECT: muscle contraction. Also found in the brain, and associated with addiction.

GABA_A receptors. LIGAND: GABA (y-amino butyric acid) LOCATION: Neurones PHYSIOLOGICAL EFFECT: dampen down the function of the brain. Lowers neuronal excitability in the CNS.

Question 23

What does the Greek letter, gamma look like?

Answer 23

Looks like a ‘y’.

Question 24

What is the G-protein receptor composed of in resting state?

Answer 24

G-protein is a heterotrimeric complex. Made of alpha, beta and gamma sub-units. Alpha is bound to internal side of membrane. Beta and gamma subunits are always bound to each other (called beta-gamma subunit as a result). GDP is associated with G-protein. G-protein receptor has nothing bound.

Question 25

How does G-protein coupled receptor work?

Answer 25

Binding of a ligand or hormone. Activates a signal inside the cell via an intracellular G-protein. Receptor also known as a 7-TM receptor. 1. Ligand binding to G-protein receptor. 2. Receptor activated and there is conformational change so that the internal region of the receptor is available for binding by the G-protein – because it now requires less energy to bind (remember, this is physics). 3. GDP molecule is EXCHANGED for a GTP. 4. This provides the energy that allows the alpha subunit to dissociate from the beta-gamma subunit. 5. Alpha subunit (GTP molecule still bound) binds to the target protein. Target protein is activated which starts the whole cascade of events intracellularly.

Question 26

How is this signalling stopped? (x3 steps)

Answer 26

1. Internal GTPase activity on alpha subunit dephosphorylates GTP to GDP. 2. Alpha subunit dissociates from target protein because no longer energetically favourable. Target protein inactivated. 3. Receptor inactive when ligand is unbound.

Question 27

What are the three main types of alpha subunit receptors? (include one example for each).

Answer 27

[this covers the ‘examples of intracellular signalling’ point]
G_s protein linked receptor (“G-alpha-s-protein-sub-unit”):
STIMULATES ADENYLYL CYCLASE: Converts ATP to cAMP. cAMP activates protein kinase A (PKA).
e.g. β₁-adrenergic receptor on heart which increases heart rate. Sympathetic N-S.

G_i protein linked receptor: (exact opposite function).

• *I**NHIBITS ADENYLYL CYCLASE: Reduced PKA levels.
  e. g. M₂-muscarinic receptor on heart decreases heart rate. Parasympathetic N-S.

G_q protein linked receptor (“G-alpha-q-protein-sub-unit”):
STIMULATES PHOSPHOLIPASE: Converts PIP₂ to IP₃ and DAG. IP₃ stimulates Ca²⁺ release. DAG activates PKC.
e.g. AT-1 angiotensin receptor which results in vasoconstriction of smooth muscle.

Question 28

How does the enzyme-linked receptor work?

Answer 28

Important difference is that there are more than one protein receptors involved. 1. Ligand binding to each receptor. Causes the receptors to cluster. 2. This activates enzyme activity within the cytoplasmic domain (the part of the receptor INSIDE the cell). 3. Enzymes phosphorylate the receptor which results in binding of signalling proteins to the cytoplasmic domain. [photo]. 4. These proteins signal other signalling proteins and a signal is generated within the cell.

Question 29

Examples of enzyme-linked receptors? (x2 including categories for each)

Answer 29

One type of receptor is Tyrosine kinase enzyme-linked receptors. There are many examples; here is one: Insulin receptor (CD220 antigen): LIGAND: Insulin PHYSIOLOGICAL EFFECT: glucose uptake. Another type: Guanylyl-cyclase lined receptors: e.g. NPRA LIGAND: atrial/brain natriuretic peptide. PHYSIOLOGICAL EFFECTS: Vasodilation and decreased blood pressure.

Question 30

What are the two intracellular receptor types?

Answer 30

Type 1 = CYTOPLASMIC – receptor located in the cytosolic compartment i.e. not in the nucleus. Type 2 = NUCLEAR – receptor located within the nucleus.

Question 31

How do cytoplasmic intracellular receptors work?

Answer 31

1. Associated with heat shock proteins (hsp). 2. Hormone binds to receptor and hsp dissociates (remember, only certain hormones can cross the membrane). 3. 2 hormone bound receptors cluster to form a homodimer. 4. The homodimer translocates (move) to the nucleus and bind to the DNA.

Question 32

According to the mechanism of cytoplasmic intracellular receptor, what is the purpose of action of the receptors?

Answer 32

Action of receptors is to change the transcription of the protein products produced by the DNA.

Question 33

Time scale of the effects of cytoplasmic intracellular receptor activation?

Answer 33

Very slow because they rely on the effects of changing transcription of a cell’s protein products. Takes a while to accumulate and have an effect.

Question 34

How do nucleic intracellular receptors work?

Answer 34

Binding of the hormone ligand directly results in regulation of DNA transcription (because receptor already bound in nucleus.

Question 35

Example of Type 1 intracellular receptor?

Answer 35

Glucocorticoid receptor. LIGANDS: cortisol, corticosterone. PHYSIOLOGICAL EFFECT: lowered immune response and raise gluconeogenesis.

Question 36

Example of Type 2 intracellular receptor?

Answer 36

Thyroid hormone receptor. LIGAND: Thyroxine (T4), triiodothyronine (T3). PHYSIOLOGICAL EFFECT: growth and development.