• a dimer
• ZA connector protein 
• function is Ca2+ dependent.
• There are many diff. types of cadherins – over 8- in humans. They all adhere (strongest intercellular binding proteins in humans), but some have other functions – such as protein kinese cadherins which are in signal transduction – this one is not homophilic.
• Cells can turn off cadherin expression if they need to migrate – as in development (neural tubes- N-cadherin), then re-expresse Cadherin when reaches destination.

• Tight junctions – looks like a quilt in EM
• can’t form unless ZA has already formed (in development).
• Separates apical and basal regions, do not allow proteins and outer leaflet membrane lipids cannot pass (there are diff. things in each PM).
• Prevent molecules from going b/w cells (paracellular) – essential in gut and bladder and in blood brain barrier. Other junctions are looser. Drug research is trying to loosen ZO to permit drug entry via the paracellular pathway.
• Connects to actin filaments

• Freeze fracture- cleaves b/w the 2 membranes
  • E-face – extracellular – you are looking at the inside of the outer membrane
  • P-face – protoplasmic- grooves- extended look- you are looking at the outside of inner membrane
  • Can see 2 diff. faces – b/c 2 diff cells – normally not seen.

• Spot-welds – function is tensile strength – protect from tearing (like in the skin)
• Connect IF systems (keratins in epithelia)
• Exists in epithelia, cardiac muscle, brain, and others.

• Not connected to the cytoskeleton
• Not an adhesion connection-  instead communication (chemical and electrical)- tunnels
• Passage for cAMP, CA2+, inositol triphosphates (signaling molecules) and also glucose - up to 1000 MW? 2000? 1500?
• Epithelia and heart and neurons (electrical synapsis) 
•         Gap junctions can be used to provide nutrition, nourishment of the oocyte(dosen’t have direct access to glucose and is surrounded by granulosa cells) is dependent on gap junctions from the granulosa cells

• actin-binding proteins (ex:vinculin) bind to adapter proteins (catenins)that bind to transmembrane adhesion proteins (cadherins – in epithelia- E-cadherins) that bind to an op. transmembrane protein that’s homophilic (the attached molecule is identical) and so on (E-cadherins will only bind to E-cadherins)
• The actin is cross-linked by alpha-actinin - the MF are identically oriented- parallel.

• Connexin 43 – granulosa cells communicate amongst themselves
• Connexon 37- granulose cells communicate with the oocyte

Ca2+ can close the gap junctions- imp because high cytoplasmic cA2+ is consistent with cellular injury that would want to contain

•   Dopamine- closes the gap junctions

• research:
• Uses regulation, isolation of culture of rate cardiomyocytes- hard isolation- Ca2+ will kill the cell when isolating, but it is necessary- found a chemical that will close the gap junctions so that can isolate with Ca2+ so to keep the cells alive

• connect IF of epithelial cells to extracellular proteins in the basal lamina (connect to dermis) via transmembrane, ECM receptors called integrins
• No homophilic binding
• in the PM – they look like half a desmosome
• Connect to the basement membrane for a long period – only put in when want stability
• Function – provide a strong bond, end result of problems – still blisters
• Both desmosomes and hemidesmosomes show plaques in the EM (dark areas next to the PM) because they bind heavy metals well.
• Skin is the tissue that hemidesmosomes are the most imp., but that is not the only place where hemidesmosomes problems exist. Only in epithelia.

• Integrins have 2 subunits – alpha and beta, Each subunit represents a family, so many combinations. Alpha6beta4 integrins (heterodimers) – adaptor proteins – specific to hemidesmosomes and bind extracellular laminin and fibronectin
  • Integrins have low binding affinities are present in lg. #s
  • Transmembrane
• Plectin- adaptor for IF to integrins, but also cross-links IF to IFs, to MF’s, and to MT, a mutation in plectin will cause the most serious blistering disease- variants of epidermolysis bullosa

• Connects actin cytoskeleton of the cell to extracellular proteins in the basal lamina via integrins (also in HD- difference is in the alpha and beta subunits).
• Helps shape the cell – the actin filaments (Stress fibers) can be pulled together
• MT and actin interact via FC. MT are brought to the FC by elongation or by motors, and then they depolymerize and pull back. This interaction is imp. for signaling the movement of cell
• Fibroblasts and migrating cells (mast cells and macrophages) may only temporarily possess focal contacts
• Can be stable or dynamic – can be used in motility
• Highly regulated- Signals regulate integrin aggregation, adhesion, and the release of connections.
• Kinases, phosphorlase- how they can be regulated
• Actin filament bundles- terminate at the focal adhesion sites – shown in a culture- focal adhesions allow the cell to attach to the plastic, otherwise they would die, so proteins in focal contacts convey info. to allow to cell to decide whether to do apoptosis

• Bind to fibronectin or laminin at the RGD sequence – to the extracellular matrix
• Vinculin and talin and alpha actinin– actin-binding proteins
• Integrins-  both subunits bind to the EC matrix, composed of alpha and beta subunits
• Focal-adhesion kinases(FAK) or c-src- signaling molecules in the focal contact – can increase the size of the focal adhesion

• (lectin is a protein that binds sugars)
• expressed on: Lymphocyte, Endothelial cellPlatelet(and stimulated endothelium)
• Binds carbohydrate residues on other cells, weaker than cadherins
• When expressed on vascular endothelial cells, P-selectin when activated by cytokines bind a polysaccharide on a leukocyte surface to slow them
• Transmembrane and attached to cytoskeleton

• ICAM1, ICAM2, VCAM
• Any cell can express CAMs
• Some are floating free an don’t have a transmembrane portion – much variability
• Promote binding b/w endothelial cells and integrins on leukocytes  - this stops them so they can migrate to the extravascular space. They may also bind to themselves.

1. A trauma occurs that attracts macrophages or other leukocytes to a subendothelial site
2. They release inflammatory cytokines that are detected by endothelial cells.
3. Endothelial cells “secrete” P-selectin (E-selectin is constitutively expressed)
4. P-selectin binds to a carbohydrate on a leukocyte PSGL-1
5. Cytokines cause activation of leukocyte integrins – this slows it down
6. Leukocyte integrins bind to ICAMS on endothelial cells, tight binding which stops it
7. Bound leukocyte interacts with endothelial cells- loosens TJ- and passes in-between them extravasation.