Cell Signalling and Communication

Cell Signalling

• Cell signalling is the communication between cells, involving a chemical messenger (signal/ligand) released by the signalling cell.
• The signal is detected by the responding cell (receptor), triggering intracellular reactions that influence the behaviour of the responding cell.

Tasks of Cell Communication

• Signal release: synthesis and excretion of the signalling molecule by the signalling cell.
• Signal detection: interaction of signal and receptor.
• Signal transduction: translation of detection to changes in cell physiology or gene expression.

Types of Signals

• Paracrine signals: act on a local set of cells.
• Autocrine signals: act on the secreting cell itself.
• Endocrine signals: long-range signals moving through the bloodstream.

Signalling and Control of Gene Expression

• Cell-cell signalling can change the repertoire of transcription factors in the responding cell, resulting in different gene expression.
• Some signals can form gradients, and cell fate depends on signal concentration.

Signal Entry into the Cell

• Two strategies for signal entry:
  • The signal can pass through the plasma membrane (e.g., nuclear receptors).
  • The signal can activate a membrane receptor (e.g., G protein linked receptors, Serine/threonine kinase receptors).

Nuclear Receptors

• Signals are steroids or retinoids.
• These signals can pass through the plasma membrane and encounter nuclear receptors in the cytoplasm.
• The receptor-ligand complex then enters the nucleus to activate genes.

Signalling through Nuclear Receptors

• Nuclear receptors like the glucocorticoid receptor are cytoplasmic proteins.
• In their inactive form, they are bound to Hsp chaperones.
• Ligand binding releases the Hsp, and the receptor-ligand complex moves to the nucleus to activate the transcription of target genes.

G-Protein Linked Receptors

• Transmembrane receptors are linked to a G-protein.
• Upon ligand binding, the G protein releases GDP and takes up GTP.
• Ga dissociates from Gbg and activates downstream 'second messengers' (e.g., cAMP).
• GTP is hydrolyzed to GDP, and Ga reassociates with Gbg.

Serine/Threonine Kinase Receptors

• Transmembrane receptors that bind the TGFb family of signals.
• Ligand brings together type I and type II receptors.
• Type II phosphorylates type I.
• Smads become phosphorylated and move into the nucleus to act as transcription factors.

Membrane Selective Permeability

• Membranes define a barrier between the inside and outside of a cell, and the inside must interact with the outside.
• Examples of selective permeability include:
  • Bulk transfer by endo and exocytosis
  • Secreting and importing proteins
  • Solute molecules, such as ions (e.g. Na+, K+, Cl-) and metabolites (e.g. sugars, amino acids)

Transport Across the Membrane

• Simple diffusion:
  • Occurs down a concentration gradient towards equilibrium
  • Small, uncharged polar molecules can diffuse across the membrane best
• Osmosis:
  • A special case of simple diffusion where water is diffused
  • The plasma membrane is highly permeable to water
• Facilitated diffusion:
  • Larger and/or polar molecules are helped across the membrane
  • Two types of integral membrane proteins involved: carrier proteins and channel proteins
• Active transport:
  • Moves molecules against a concentration gradient
  • Divided into direct active transport (uses ATP hydrolysis) and indirect transport (uses co-transport of a solute favorably down its gradient)

Bulk Transfer

• Endo and exocytosis are forms of bulk transfer

Ion Concentrations

• The cytosolic pH is maintained at around 7.2 by regulating hydrogen ion concentration
• K+ is generally higher intracellular than extracellular
• Na+ is generally lower intracellular than extracellular
• Direct ATP-powered pumps maintain an ionic gradient across the membrane

Synthesis of the Membrane

• Cells synthesise new membranes by expanding existing membranes
• Lipid precursors are synthesised in the cytosol and ER
• Membrane lipids are distributed to target membranes by vesicles and vesicle-independent mechanisms

Membrane Structure and Composition

• Varying lipid composition alters membrane physical properties
• Fluidity depends on the ratio of saturated to unsaturated fatty acids and fatty acid tail length
• Cholesterol affects fluidity by preventing it from becoming too fluid or too crystalline

Lipid Bilayer

• The lipid bilayer is fluid, with lipids able to move laterally but not flip into the opposing layer
• Long-chain fatty acids pack against each other, stabilized by van der Waals forces
• The longer the chain, the less fluidity the lipid has in the membrane

Leaflets and Flippases

• The two layers of the lipid bilayer are referred to as leaflets, which often have different lipid compositions
• Moving from one leaflet to another is a slower process than lateral movement within a leaflet, facilitated by integral membrane proteins called flippases

Proteins in the Lipid Bilayer

• Proteins float in the lipid bilayer, representing the mosaic part of the fluid mosaic model of membrane structure
• There are three main groups of proteins associated with the lipid bilayer: lipid-anchored, peripheral, and integral membrane proteins

Asymmetry of the Lipid Bilayer

• The layers of the lipid bilayer can be asymmetric in lipid and protein composition
• Some proteins are mobile in their layer, while others are anchored to the cytoskeleton or extracellular matrix

Cell Wall and Cytoskeleton

• The cell wall is a rigid structure surrounding plant and some fungal cells, composed of cellulose microfibrils embedded in pectin and hemicellulose
• The plasma membrane is associated with the cell wall
• The cytoskeleton is an array of filaments beneath the plasma membrane, providing support to the cell

Membrane Functions

• Membranes define cells and organelles within cells
• Membranes regulate the transport of solutes, detect and transmit electrical and chemical signals, and provide surfaces for reactions

Biomembranes

• Biomembranes are composed of lipid bilayers
• Lipids found in cell membranes are amphipathic, with a polar head and non-polar tail
• Amphipathic lipids spontaneously form lipid bilayers with hydrophilic heads facing the aqueous solution and hydrophobic tails stacking upon themselves

Lipid Classes

• Examples of amphipathic membrane lipids include phosphoglycerides, sphingolipids, and cholesterol
• Lipids are important for membranes, energy storage, and cell signaling
• Phospholipids, glycolipids, and cholesterol are the main classes of membrane lipids