Communication between cells

Question 1

Explain the physiological functions of cell signaling and list examples of intercellular and intracellular signaling

Answer 1

Physiological functions;

1. Process information
2. Self-preservation
3. Voluntary movement
4. Homeostasis
   
   • Thermoregulation
   • Glucose homeostasis
5. Communication methods
   
   • Nervous system
   • vasculature

Example of communication between tissues and within a tissue

Hyperglycaemia; (physiological respone)

1. Reduced gluconeogenesis
2. Reduced glycogenolysis
3. Insulin released in response to hyperglycaemia;
4. From b- cells in the Islets of Langerhans
5. Halts release of glucagon

Hypoglycaemia; (physiological response)

1. Gluconeogenesis
2. Glycogenolysis
3. Both mediated by Glucagon- released in response to hypoglycaemia from a-cells of Islets of Langerhans and stimualtes liver

Question 2

Explain, with examples, modes of intercellular signaling including, endocrine, paracrine, autocrine, and signaling by membrane attached proteins

Answer 2

Endocrine; Hormone travels within blood vessel to act on a distant target cell

• Andrenaline acts on trachea
• Insulin from pancreas acts on liver, adipose tissue and muscles

Autocrine; Signalling molecule acts on same cell

• Ach having binding to mAchR in pre-synaptic terminal

Paracrine; Hormone acts on adjacent cells

• Osteoclast activating factors produced by adjacent osteoblasts
• NO produced by endothelial cells acting on smooth muscle

Signaling by membrane attached proteins; Plasma membrane proteins on adjacent cells interacting

• Engagement of T-cell and MHC through TCR

Question 3

List examples of physiological processes regulated by ionotropic receptors

Answer 3

1. Nicotinic Acetylcholine receptor (nAchR)
   
   • Ligand: Acetylcholine (ACh)
   • Location: Skeletal muscle
   • Physiological effect: Muscle contraction
2. GABAA
   
   • Ligand: g-amino butyric acid (GABA)
   • Location: Neuronal
   • Physiological effect: decreased neuronal excitability

Question 4

Explain the mechanisms of enzyme-linked receptor actions and provide examples of physiological processes regulated by enzyme-linked receptors.

Answer 4

1. Ligand binding –> receptors clustering
2. Receptor clustering activates enzyme activity within cytoplasmic domain
3. Enzymes phosphorylate receptor
   
   • Phosphorylation –> binding of signalling proteins to cytoplasmic domain
4. These signalling proteins recruit other signalling proteins and the signal is generated within cell (Outside-inside signalling with cascade)

ex.

• Insulin receptor (CD220 antigen)
• Ligand: Insulin
• Physiological effect: Glucose uptake

Question 5

Explain the mechanisms of intracellular receptor actions and provide examples of physiological processes regulated by intracellular receptors.

Answer 5

For steroid hormones (lipid soluble), act as transcription factors

Type 1 - Cytoplasmic

1. Located within the cytosolic compartment
2. Associated with chaperone molecules (heat shock proteins, hsp)
3. Hormone binds to receptor –> hsp dissociates
4. 2 hormone bound receptors form a homodimer.
5. The homodimer translocates to the nucleus and binds to DNA

ex.

Type 1 - Glucocorticoid receptor

• Ligands: Cortisol, corticosterone
• Physiological effect: decreased immune response and increased Gluconeogenesis

Type 2 - Nuclear

1. Located within the nucleus
2. Binding of hormone ligand leading to transcriptional regulation

ex.

Type 2 - Thyroid hormone receptor

• Ligand: Thyroxine (T4), triiodothyronine (T3)
• Physiological effect: Growth & development

Question 6

Explain the mechanisms of G-protein action in signal transduction and provide examples of physiological processes regulated by G-protein coupled receptors

Answer 6

Signaling transduction events:

1. 7-TM receptor & heterotrimeric G-protein are inactive
2. Ligand binding changes conformation of receptor
3. Unassociated G-protein binds to the receptor and GDP is exchanged for GTP
4. G-protein dissociates into two active components:
   
   1. a-subunit
   2. bg subunit which are going to bind to their target proteins
5. Internal GTPase activity on a-subunit dephosphorylates GTP into GDP
6. a-subunit dissociates from target protein and becomes inactive again
7. Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins

ex Gi protein linked receptor

• Inhibits adenylyl cyclase
• Reduces levels of PKA
• Example: M2-muscarinic receptor
• Effect: decreased heart rate