Week 7 - Endocrine System 1: Cell Signalling

7 categories of PROTEINS

1. Enzymes - catalyse biochemical reactions (e.g lactase)

2. Membrane transporters - e.g channel proteins

3. Signal molecules - attach to receptors (e.g neurotransmitters)

4. Receptors - Provide attachment sites for signal molecules

5. Binding proteins - Found in extracellular fluid, bind and transport molecules (e.g hemoglobin)

6. Immunoglobulins/antibodies - Provide immune response

7. Regulatory proteins - Increase or decrease cellular processes (e.g transcription factors)

Local signalling

• Gap junctions

• Contact-dependent

• Paracrine signalling

• Autocrine signalling

Long distance communication

• Nervous system - Electrical

  • Neurotransmitters

  • Neurohormones

• Endocrine system - Chemical

  • Hormones

• Immune system - Chemical

  • Cytokines

Communication occurs within own or adjacent cells.

Gap junctions: Signals are sent through gap junctions (think cardiomyocytes & action potential propagation) ← CHEMICAL ARE NOT SENT INTO ECF, HENCE NOT A CHEMICAL SIGNAL

Contact-dependent: Signals occur through signal molecules & receptors, requiring brief and direct contact between separate cells ← CHEMICAL ARE NOT SENT INTO ECF, HENCE NOT A CHEMICAL SIGNAL

Paracrine signalling: Chemicals are secreted into ECF and bind to receptors of adjacent cells

Autocrine signalling: Chemicals are secreted into ECF and bind to receptors of own cell — Self-signalling

• Some molecules can cause both paracrine & autocrine signals

Local signalling

• Gap junctions

• Contact-dependent signals

• Paracrine signalling

• Autocrine signalling

Long distance communication

• Nervous system - Electrical

  • Neurotransmitters

  • Neurohormones

• Endocrine system - Chemical

  • Hormones

• Immune system - Chemical

  • Cytokines

Nervous system:

Neurotransmitters are sent directly from a neuron to a target cell, causing depolarisation.

Neurohormones travel through the blood before arriving to the target cell (which has a specialised receptor) and causing depolarisation.

Local signalling

• Gap junctions

• Contact-dependent signals

• Paracrine signalling

• Autocrine signalling

Long distance communication

• Nervous system - Electrical

  • Neurotransmitters

  • Neurohormones

• Endocrine system - Chemical

  • Hormones

• Immune system - Chemical

  • Cytokines

Endocrine system:

Hormones are sent from endocrine cells/glands and travel through the blood before arriving to a cell with a specialised receptor, names a target cell, leading to cell response.

Local signalling

• Gap junctions

• Contact-dependent signals

• Paracrine signalling

• Autocrine signalling

Long distance communication

• Nervous system - Electrical

  • Neurotransmitters

  • Neurohormones

• Endocrine system - Chemical

  • Hormones

• Immune system - Chemical

  • Cytokines

Cells release cytokines which cause an immune response.

2 main CELL SIGNAL PATHWAYS

1. Electrical signals: Changes in cell membrane potential (NERVOUS SYSTEM)

2. Chemical signals: Molecules secreted into extracellular fluid (ECF) send signals (ENDOCRINE SYSTEM)

   1. Send signals to target cells

CELL SIGNAL PATHWAY breakdown:

First messenger → Protein receptor → Intracellular signal molecules → Cell response

1. Signal molecule/ligand brings external stimuli to target cell, binding to a protein receptor — also called a first messenger

2. Binding of ligand-receptor complex activates protein receptor

3. Activated protein receptor causes a cascade, activating one or more intracellular signal molecules

4. Final signal molecule/final messenger causes cell response → protein modification or protein synthesis

CELL SIGNAL PROPAGATION: Non-protein signal molecules 3 TYPES

1. Calcium — can alters enzyme activity or initiate action potentials

2. Soluble gases (Nitric oxide, carbon monoxide, hydrogen sulfide) — can impact respiration

3. Lipids

CELL SIGNAL RECEPTION: Protein receptor 3 LOCATIONS

1. Extracellularly on cell membrane: Lipophobic signal molecules that CANNOT diffuse through the phospholipid bilayer → RAPID cellular response

2. Intracellularly within cell cytosol or cell nucleus (3): Lipophillic signal molecules that CAN diffuse through the phospholipid bilayer → modifies gene activity, SLOWER RESPONSE

BOTH RECEPTION TYPES CAN OCCUR IN TANDEM

CELL SIGNAL RECEPTION: Protein receptor 4 TYPES

1. Receptor channel — first messenger binding opens channel allowing passage of molecules in or out of the cell

2. G-protein coupled receptor (GPRC) — first messenger binding influences inner protein studded on cell membrane to open ion channels or change enzyme activity

3. Receptor-enzyme — first messenger binding activated an intracellular enzyme

4. Integrin receptor — first messenger binding alters inner enzymes or cytoskeleton

CELL SIGNAL TRANSDUCTION: Intracellular signal molecules 2 forms

1. Signal cascade — Conga line of signal molecules and activated proteins until last messenger activated conversion of a substrate into a product

2. Signal amplification — First ligand-receptor complex activated an amplifier enzyme, which propagates the signal to many intracellular molecules ← small signal, BIG response

BOTH TRANSDUCTION TYPES CAN OCCUR IN TANDEM

CELL SIGNAL REGULATION: Specificity & competition

Competition: Multiple ligands can bind to a single receptor type

• Primary ligand: Original signal molecule that activates receptor

• Agonist ligand: Additional signal molecule that also activates receptor

• Antagonist ligand: Signal molecule that also deactivates receptor

CELL SIGNAL REGULATION: Isoforms

Isoforms: Multiple receptors can be activated by the same ligand

• Each receptor type leads to different cellular response, thus are often located in different locations

CELL SIGNAL REGULATION: Saturation

Saturation: Maximum activity level within a cell due to the finite number of receptor proteins with each cell.

• Downregulation: Decrease in no. receptors, hence lower saturation

  • Can be done by:

    • Physical removal of receptor proteins via endocytosis

    • Desensitisation via attachment of chemical modulators/antagonist ligands (e.g phosphorylation)

• Upregulation: Increase in no. receptors, hence higher saturation

CELL SIGNAL TERMINATION

First messenger can be:

• Degraded by extracellular enzymes

• Transported into neighbouring cells

• Endocytosis of the entire receptor-ligand complex

  • Intracellularly, ligand is removed and the receptors can be returned to the membrane by exocytosis

Reflex pathways: HOMEOSTASIS in long-distance pathways

Occurs in endocrine, nervous & immune systems

Reflex pathways: Stimulus

A disturbance/change in the environment that initiates the reflex pathway to occur. Often when values fall out of the homeostatic range.

Reflex pathways: Receptor/Sensor

Continuously monitors the environment via tonic control, senses change from a stimulus. Propagates an input signal towards a integrating centre.

• Two forms of receptors:

  • Proteins studded on cell membranes/inside cells

  • Cells that sense specific stimuli (e.g mechanoreceptors, chemoreceptors, etc.)

Reflex pathways: Integrating centre

Cells that compare the input signals’s value, give from sensors/receptors, with homeostatic values (setpoints). If variable has moved outside of normal range, sends an output signal.

• Can receive multiple signals at once and must prioritise

Reflex pathways: Target & Response

Receives the output signal and carries out appropriate response to either return to homeostasis (negative feedback loop) or propagate further away from normal values (positive feedback loop).

3 Types of response:

1. Cellular response

2. Tissue/organ response

3. General systemic response

Written in order of magnitude.

Reflex pathways: Endocrine system

Input & Integration:

Stimulus acts directly on endocrine cells.

Thus, endocrine cells are both the sensor & integrating centres.

Output:

All output signals are transmitted through hormones by BLOOD.

Simple vs Complex reflex pathways

Simple: Entire pathways is either ONLY NEURAL or ONLY ENDOCRINE

Complex: COMBINE NEURAL & ENDOCRINE pathways

• Neural & endocrine systems pathways work in tandem, on a continuum