Direct Cell-Cell Signalling Flashcards
What are Gap Junctions?
Direct cell-cell contact via formation of a cytoplasmic bridge
What is the gap distance separating two adjacent cells at Gap Junctions?
2-5 nm
What is the shape of the Gap Junction channel?
Hexagonal
What is the name of the proteins that make up Gap Junction channels?
Connexins
What do Gap Junctions allow the direct movement of between the cytoplasms of adjacent cells?
Inorganic ions and small water-soluble molecules
What is the structure of Connexin?
Four-Pass Transmembrane Proteins with N- and C-termini at the cytoplasmic side
How many Connexin molecules of one plasma membrane form the hexagonal cylinder of a Gap Junction?
6
What is the diameter of a Gap Junction?
1-2 nm
What is the hexagonal cylinder of a Gap Junction known as?
Connexon
How many Connexin isoforms are present in vertebrates?
Over 20
What are Homotypic Channels?
Single isoform type of Connexin
TRUE OR FALSE:
Most cells express at least two connexins
True.
Assemble into Hetero-Oligomeric Connexons creating Heterotypic Channels
What does the diversity in Connexon channel composition lead to?
Differences in channel permeability to various molecules
What are THREE examples of diseases that mutations in the connexin gene cause?
- Neurosensory deafness
- Cataract or heart malformations
- X-linked Charcot-Marie-Tooth
Do Gap Junctions undergo reversible or irreversible conformational changes in response to changes in the cell?
Reversible.
E.g. large influx of Ca2+ from extracellular matrix into damaged cell causes gap junction channels to immediately close
What are THREE functions of Gap Junctions?
- Movement of ions
- Movement of metabolites
- Movement of secondary messengers
How does the movement of ions across gap junctions affect an Electrical Synapse?
Permit extremely rapid and reliable transmission of signals between neurons
How does the movement of ions across gap junctions affect a Muscle Contraction?
Important in propagation of depolarisation from the pacemaker of the heart to cardiac muscle cells that causes a heart contraction
What is the reason for diffusion of metabolites through gap junctions?
Ensure metabolites are shared between coupled cells
How was movement of metabolites through gap junctions demonstrated?
Co-culture of normal cell-line with mutant one lacking the enzyme thymidine kinase, and therefore unable to incorporate radioactive thymidine (tracer) into their DNA
What is the reason for movement of secondary messengers through gap junctions?
Permits propagation of signals through coupled cells
What is an example of the movement of secondary metabolites through gap junctions?
- Beating of cilia of respiratory epithelial cells spreads as synchronised waves in a cell monolayer
- Coupling is mediated by passage of IP3 through gap junctions
What is an example of experimental evidence for the permeability of Gap Junctions?
Antibodies against connexins can block intercellular communication when micro-injected into coupled cells