Week 1

• Signalling systems are needed to coordinate the activities of cells and tissues in a multi-cellular organism
• Why arre signalling systems needed?

  • Neurotransmission
  • Coordination of developmental processes (from cells to an organism)
  • Homeostasis (maintenance of a constant internal balance)
• Types of signalling between cells:

  1. Free diffusion between cells

  2. Via cytoplasmic connections

  3. Direct cell-to-cell contact
• Signalling by free diffusion is classified into three types based on distances involved:

  • Autocrine: Signalling and reception by the same cell
  • Paracrine: Signalling between nearby cells (cluster of cells)
  • Endocrine: Signalling between distant cells (by 'hormones') in the blood
• Autocrine signalling:

  • The cell secretes chemicals that modify its own behaviour
  • Often associated with cell cycle and growth regulation (negative or positive)
• Paracrine signalling:

  • Cell signalling to neighbouring cells
  • Effects are local and short-lived
  • Important in coordinating the actions of neighbouring cells in embryonic development
• Synaptic signalling:

  • A highly specific and localized type of paracrine signalling between two nerve cells or between a nerve cell and a muscle cell
• Endocrine signalling:

  • Ductless glands called endocrine glands secrete hormones into extracellular spaces, which then diffuse into the circulatory system
  • Examples: Pituitary gland, Adrenal gland, Thyroid gland
• Signalling via cytoplasmic connections involves:

  • Transfer of signal from one cell to its neighbour through pores in the membrane (gap junction in animals or plasmodesmata in plants)
  • The fastest mode of cell-cell communication
  • Example: Muscle cells in the heart communicate with each other via gap junctions, allowing all heart cells to contract almost simultaneously
• Signalling by cell-to-cell contact:

  • Involves specific interactions between surface molecules on one cell and receptors on another cell
  • Responsible for cell-cell recognition in animals
  • Important in embryonic development and immune response
• Types of signalling molecules:

  1. Local regulators – act on cells in the near vicinity (autocrine & paracrine signalling)

  2. Hormones – act at a distance (endocrine signalling)
• Growth factor – Local regulator:

  • Peptides or proteins that stimulate cell proliferation
  • Example: Nerve Growth Factor (NGF) – regulates growth of target neurons
• Gases – Local regulator:

  • Example: Nitric oxide (NO) acts as a paracrine signal molecule (1-5 sec half life)
  • Synthesized from arginine by nitric oxide synthase
  • Induces vasodilation in the cardiovascular system
• Prostaglandins – Local regulators:

  • Modified fatty acids with multiple functions
  • Example functions: Excitability of the uterine wall during childbirth, induction of fever and inflammation in the immune system
• Neurotransmitters – Local regulators:

  • Some neurotransmitters are inhibitory, some are excitatory, and some can be either
  • Examples: Acetylcholine, Biogenic amines (e.g. serotonin), Amino acids (e.g. Glutamate), Neuropeptides (e.g. endorphins)
• Hormones:

  • Long-distance signalling molecules secreted by endocrine glands and transported in the bloodstream
  • Hormone production controlled by the neuroendocrine system (hypothalamus is the control centre)
• Simple endocrine pathway:

  • Negative feedback loop
  • Example: S cells of duodenum release secretin in response to a change in internal or external variable (stimulus), which triggers the release of bicarbonate in the duodenum
• Homeostasis:

  • Maintenance of a relatively stable internal environment in the face of stress from external and internal environments
  • Dynamic equilibrium where changes are kept within an acceptable range by negative feedback loops
• Homeostasis of blood glucose through negative feedback loops:

  • Hyperglycemic (high sugar): Beta cells of pancreas stimulated to release insulin
  • Hypoglycemic (low sugar): Alpha cells release glucagon
• Two main classes of hormones:

  1. Peptides and proteins – large molecules

  2. Steroids
• Peptides and proteins as hormones (e.g. insulin):

  • Bind to receptors on the cell surface
  • Trigger events within the cell cytoplasm through second messengers
• Steroids as hormones (e.g. Testosterone):

  • Manufactured from cholesterol
  • Can pass across the lipid bilayer of the plasma membrane and bind to receptors within the cell
• Signal transduction:

  • The conversion of a signal at the cell surface to a specific cellular response through a multi-step process termed a signal transduction pathway
  • Involves reception of the signal at cell surface, transduction of the signal, and cellular response stages
• Signal transduction – signal specificity:

  • Different kinds of cells have different collections of proteins, giving each cell specificity in detecting and responding to signals
  • Pathway branching and 'cross-talk' further help coordinate incoming signals
• Receptors:

  • Three stages of cell signalling: Reception, Transduction, Response
  • Reception involves the detection of a signal (ligand) by the cell from outside the cell
• Ligands:

  • Small molecules that bind to larger molecules (receptors)
  • Ligand binding can lead to changes in protein shape or aggregation of receptors, enabling interaction with other molecules
• Reception - occurs at the cell membrane
• Transduction - involves several steps in a pathway
• Response - can be any cellular activity, such as transcription of specific genes in the nucleus or re-organization of the cytoskeleton
• Receptors in the plasma membrane:

  Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane
• Three main types of membrane receptors are G protein-coupled receptors, receptor tyrosine kinases, and ion channel receptors
• G protein-coupled receptors (GPCRs):
• GPCRs are the largest family of cell-surface receptors, with approximately 1000 encoded in the human genome
• GPCRs span the plasma membrane with seven alpha helices
• G proteins work with GPCRs
• G proteins are heterotrimeric with alpha, beta, and gamma subunits
• G proteins act as a molecular switch, being either on or off depending on whether GDP or GTP is bound
• When a signaling molecule binds to a GPCR, receptor activation occurs, leading to G protein activation and subsequent cellular response
• Epinephrine or adrenaline stimulates glycogen breakdown in the liver and skeletal muscle during stress
• Bacterial diseases like whooping cough, cholera, and botulism interfere with normal G protein-coupled receptor function