Direct Cell-Cell Signalling and Gap Junctions

What can signalling influence cells to do?

1. cell survival and cell division

2. cell differentiation

3. morphogenesis

4. apoptosis

two main types of signalling

1. direct cell signalling

2. indirect cell signalling

   • autocrine

   • paracrine

     • ion channel coupled receptors

     • enzyme coupled receptors

     • G-protein coupled receptors

   • endocrine

molecular switches

intracellular signalling proteins

• switch on (ACTIVE) and off (INACTIVE)

• length of time they are switched on determines how long cell is responding

• for every activation step there is an inactivation step

types of molecular switches

1. proteins that influence phosphorylation status

   • kinase → PHOSPHORYLATES

   • phosphatase → DEPHOSPHORYLATES

2. GTP-binding proteins

direct cell-cell signalling

• signalling by plasma-membrane attached proteins

• cells must be touching

• bidirectional signalling via gap junctions

gap junctions equilibrium

communication via gap junctions allows equilibrium to be reached

electrochemical gradients direct the transfer of small molecules through gap junctions until an equilibrium is reached

gap junctions size restriction- what molecules can pass through?

• only small molecules can pass through (<1kDa)

  • amino acids

  • nucleotides

  • ions

structure of gap junctions

• 4 transmembrane proteins → CONNEXIN

• 6 connexins → CONNEXON (hemi junction)

• 2 connexons → GAP JUNCTION

selectivity of gap junctions

• 21 different connexin genes identified

• gap junctions made of same connexins or different combinations of connexins

• selectivity due to differences between amino acids that face the internal channel

can be selective for different charged molecules

What happens to gap junctions in most cancer cells?

gap junctions are lost

no longer undergo coordinated, regulated growth

two possible effects of gap junction communication on tumour spread and pathology

1. progression

2. suppression

example of pathology caused by loss of specific gap junctions

congenital cataracts

• lens relies on gap junctions for delivery of nutrients

• mutations cause loss of function of connexin-46 and connexin-50