intercellular communication

• communication can be done through cell junctions and plasma membrane.
• Cell junctions :

  • tight junctions
  • adherens junctions
  • desmosomes
  • hemidesmosomes
  • gap junctions
• Through plasma membrane :

  • autocrine
  • paracrine
  • endocrine
• Local signaling :

  1. autocrine [own cell]
  2. paracrine [between nearby cells ]
  3. synaptic (a form of paracrine signaling )
• Endocrine signaling occurs between cells found far away from each other .

  e.g : hormones flow in the bloodstream to the recipient cell .
• Major components of signaling :

  1. reception
  2. transduction
  3. response
• Receptor types :

  1. ligand gated channels [ion or voltage ] (LGIC are called ionotropric receptor )
  2. enzyme linked receptor
  3. G protein coupled receptor
• Ligand gated ion channels [ionotropic receptor ]:

  • transmembrane receptor
  • most receptors are pentamers (5 subunits)
  • 1 subunit = 4 transmembrane spanning regions
  • receptor is an integral part of the channel
  • channel has a ligand binding domain in the outer surface of plasma membrane and a channel forming domain that transverses the width of the membrane .
• At synapses , neurotransmitter is the ligand that binds to the receptor .

  Presynaptic : chemical signal

  Postsynaptic : electrical signal
• Ex of LGIC :

  1. Cation permeable -> Ca , Na , K and glutamate receptor .
  2. Anion permeable -> Cl , glycine receptor .
• Enzyme linked receptor :

  • Transmembrane receptor
  • Ligand binding domain -> on outer surface of plasma membrane
  • Cytosolic -> intrinsic enzyme activity
• Classes of enzyme linked receptor :

  1. receptor tyrosine kinase [RTK]
  2. tyrosine kinase associated receptor
  3. receptor serine / threonine kinase
  4. transmembrane receptor guanylcyclases
  5. receptor tyrosine phosphatase
• Receptor tyrosine kinase [RTK] :

  • They are acted upon by growth factors and hormones .

  Epidermal growth factor

  Platelet derived growth factor

  Fibroblast growth factor

  • Insulin
• RAS

  • Proteins of the RAS superfamily of monomeric GTPases
  • Helps to transmit signals from cell surface to other parts of the cell
  • RAS + GDP = Inactive
  • RAS + GTP = Active
  • GEF activates RAS
  • GAP inactivates RAS
• Signal transmission in enzyme linked receptor [RTK] :

  1. Growth factor binds to ligand binding domain .
  2. The 2 receptors dimerize .
  3. They phosphorylate each other on multiple tyrosine . This process is called autophosphorylation .
  4. This activates the tyrosine kinase domain .
  5. GRB2 with SOS bound to it , binds to the docking sites ( phosphorylated tyrosine residues) via their SH2 domain .
• 6. SOS is activated.

  7. SOS allows RAS to bind to GTP , activating it .

  8. Activated RAS causes a series of serine/ threonine phosphorylations .

  9. MAP-KKK [RAF] is phosphorylated to MAP-KK [ MEK] .

  10. MAP-KK[MEK] activates MAP-K [ ERK] .

  11. This kinase cascade amplifies the signal .

  12. MAP-K [ERK] phosphorylates gene regulatory proteins and protein kinases .