Case 1
• Brainstorm:
• Autocrine
• Paracrine
• Gap junctions
• Endocrine (Hormones)
• Direct cell-cell interactions
• Receptors and ligands
• Communication between cells close together and far away
• Neural pathways
• Wnt-pathway (Sox)
• Hedgehog (SHH) pathway
• Notch signaling
• FGF pathway
• Tight junctions (gut)(D-dimer)
Learning goals:
1. What type of different junctions exist between cells and how do they work? (tight,
gap and adherens junctions)
2. How does a cell communicate with itself?
3. How does a cell communicate with neighboring cells? (Notch signaling
4. How does a cell communicate with other cells over a short distance? (Wnt and
hedgehog signaling)
5. How do cells communicate with other cells over a longer distance?
, 1. What type of different junctions exist between cells and how do they work? (tight,
gap and adherens junctions)
1. Gap junctions (channel-forming junctions)
- Clusters of intercellular channels that allow direct diffusion of ions and small
molecules between adjacent cells.
- rapid cell-to-cell communication through cytoplasmic bridges, connexins
interlock to create passageways.
- Primary role: coordinate activity of adjacent cells (in heart, gap junctions allow
transmission of electrical signals between cells)
- The channels are able to open and close, regulating movement of small
molecules and ions through them.
o Ions (calcium ions)
o Regulatory proteins
o Metabolites
- Structure: Each gap junction channel is made
up of two half channels (hemichannels), one
in each cell’s membrane. Each of these half
channels is called a connexin which is made
up of 6 symmetrical integral membrane protein
units: connexins.
- Connexins are expressed in all tissues except
differentiated skeletal muscle, erythrocytes
(RBCs), and mature sperm cells. Most
important tissues:
o Epithelia
o Nerves
o Cardiac muscle
o Smooth muscles
(no transport of molecules larger than 5kD)
- Both chemical and electrical signals
- Many tissues (including: liver, pancreas, ovary, thyroid gland)
,2. Tight junctions (occluding junctions)
Plasma membranes of adjacent cells fuse together tightly to limit leakage of
substances between the cells.
Occluding junctions which restrict movement of
material between the cells they link. The cells
membranes partly fuse together with help of claudins
and occludins (proteins), thereby making a barrier.
Important proteins in tight junctions:
- Occludins – maintain barrier between adjacent cells
- Claudins – form backbone of tight junction strands
- Junctional adhesion molecules (JAMs) –
immunoglobulin (antibody) proteins which help seal
the intercellular space between two cells
- Zonula occludens (ZO) – proteins which help link
thight junction to each cell’s cytoskeleton
- Tricellulins – attachment when 3 cells are bound
together
- Can be altered to body’s needs
- Located in epithelia (skin, blood vessels, organs, cavities)
- Enable cells to regulate what enters and leaves the body (prevent substances
moving freely between external and internal environments in kidney and
intestines)
- Create blood-brain barrier (prevent harmful substances reaching extracellular
fluid of brain)
, 3. Anchoring junctions
Attach cells to each other (cell-cell anchoring junctions) or to the extracellular matrix
(cell-matrix anchoring junctions). Cell-cell anchoring junctions are created by CAMs
(cell adhesion molecules) called cadherins, cell-matrix junctions uses CAMs called
integrins.
- Contribute to mechanical strength of tissue, protein linkage of anchoring cell
junctions is very strong (single bond is weak but many cadherins and calcium
ions make it a strong binding between cells) because they bind to the
cytoskeleton
- Function cell-matrix junctions: Cell needs to be connected to ECM for the
resistance to external forces that could pressure onto the cells.
- Spaces between cells allow materials to pass (picket fence)
- Cell-cell (actin) anchoring junctions take form of adherens junctions or
desmosomes:
o Adherens junctions link actin fibers in adjacent cells together cadherin
(work as a anchor to bind to cells to ensure the cell does not) (type of
cadherins: E-cadherin (epithelial), P-cadherin (placenta and epidermal
cells) , M-cadhein (muscle cells)
o Desmosomes attach to intermediate filaments of the cytoskeleton
(strongest cell-cell junctions). Non-classical cadherens: desmoglein and
desmocolling
o Homophillic binding: binding between same type of cadherins
- Cell-matrix (intermediate) anchoring junctions are in 2 types:
o Hemidesmosomes anchor intermediate fibers of the cytoskeleton to
fibrous matrix proteins like laminin (+catenin, ?)
o Focal adhesions tie intracellular actin fibers to different matrix proteins
like fibronectin
• Brainstorm:
• Autocrine
• Paracrine
• Gap junctions
• Endocrine (Hormones)
• Direct cell-cell interactions
• Receptors and ligands
• Communication between cells close together and far away
• Neural pathways
• Wnt-pathway (Sox)
• Hedgehog (SHH) pathway
• Notch signaling
• FGF pathway
• Tight junctions (gut)(D-dimer)
Learning goals:
1. What type of different junctions exist between cells and how do they work? (tight,
gap and adherens junctions)
2. How does a cell communicate with itself?
3. How does a cell communicate with neighboring cells? (Notch signaling
4. How does a cell communicate with other cells over a short distance? (Wnt and
hedgehog signaling)
5. How do cells communicate with other cells over a longer distance?
, 1. What type of different junctions exist between cells and how do they work? (tight,
gap and adherens junctions)
1. Gap junctions (channel-forming junctions)
- Clusters of intercellular channels that allow direct diffusion of ions and small
molecules between adjacent cells.
- rapid cell-to-cell communication through cytoplasmic bridges, connexins
interlock to create passageways.
- Primary role: coordinate activity of adjacent cells (in heart, gap junctions allow
transmission of electrical signals between cells)
- The channels are able to open and close, regulating movement of small
molecules and ions through them.
o Ions (calcium ions)
o Regulatory proteins
o Metabolites
- Structure: Each gap junction channel is made
up of two half channels (hemichannels), one
in each cell’s membrane. Each of these half
channels is called a connexin which is made
up of 6 symmetrical integral membrane protein
units: connexins.
- Connexins are expressed in all tissues except
differentiated skeletal muscle, erythrocytes
(RBCs), and mature sperm cells. Most
important tissues:
o Epithelia
o Nerves
o Cardiac muscle
o Smooth muscles
(no transport of molecules larger than 5kD)
- Both chemical and electrical signals
- Many tissues (including: liver, pancreas, ovary, thyroid gland)
,2. Tight junctions (occluding junctions)
Plasma membranes of adjacent cells fuse together tightly to limit leakage of
substances between the cells.
Occluding junctions which restrict movement of
material between the cells they link. The cells
membranes partly fuse together with help of claudins
and occludins (proteins), thereby making a barrier.
Important proteins in tight junctions:
- Occludins – maintain barrier between adjacent cells
- Claudins – form backbone of tight junction strands
- Junctional adhesion molecules (JAMs) –
immunoglobulin (antibody) proteins which help seal
the intercellular space between two cells
- Zonula occludens (ZO) – proteins which help link
thight junction to each cell’s cytoskeleton
- Tricellulins – attachment when 3 cells are bound
together
- Can be altered to body’s needs
- Located in epithelia (skin, blood vessels, organs, cavities)
- Enable cells to regulate what enters and leaves the body (prevent substances
moving freely between external and internal environments in kidney and
intestines)
- Create blood-brain barrier (prevent harmful substances reaching extracellular
fluid of brain)
, 3. Anchoring junctions
Attach cells to each other (cell-cell anchoring junctions) or to the extracellular matrix
(cell-matrix anchoring junctions). Cell-cell anchoring junctions are created by CAMs
(cell adhesion molecules) called cadherins, cell-matrix junctions uses CAMs called
integrins.
- Contribute to mechanical strength of tissue, protein linkage of anchoring cell
junctions is very strong (single bond is weak but many cadherins and calcium
ions make it a strong binding between cells) because they bind to the
cytoskeleton
- Function cell-matrix junctions: Cell needs to be connected to ECM for the
resistance to external forces that could pressure onto the cells.
- Spaces between cells allow materials to pass (picket fence)
- Cell-cell (actin) anchoring junctions take form of adherens junctions or
desmosomes:
o Adherens junctions link actin fibers in adjacent cells together cadherin
(work as a anchor to bind to cells to ensure the cell does not) (type of
cadherins: E-cadherin (epithelial), P-cadherin (placenta and epidermal
cells) , M-cadhein (muscle cells)
o Desmosomes attach to intermediate filaments of the cytoskeleton
(strongest cell-cell junctions). Non-classical cadherens: desmoglein and
desmocolling
o Homophillic binding: binding between same type of cadherins
- Cell-matrix (intermediate) anchoring junctions are in 2 types:
o Hemidesmosomes anchor intermediate fibers of the cytoskeleton to
fibrous matrix proteins like laminin (+catenin, ?)
o Focal adhesions tie intracellular actin fibers to different matrix proteins
like fibronectin
