MBM - Cell Adhesion and The ECM II

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Terms in this set (...)

What are the families of CAM's?
1. Cadhereins
2. Immunoglobulins Family
3. Selectins
4. Integrins

Most are single-pass transmembrane.
**They have an extra-cellular domain for cell adhesion and an inter membrane for anchoring, and a cytoplasmic domain that mediates attachment to the cytoskeleton.
Cell-cell Adhesion is mostly...
Homophilic
Cell-matrix Adhesion is mostly....
Heterophilic
Cadherins
Ca++Depedant
E-Cadherin - widely expressed in endothelial cells.
Preferably homophilic, involved in interaction between teh terminal subdomains of molecules on opposite cell surfaces.

Binds molecules called alpha and beta CATENINS.
Homphilic binding by cadherins is believed to contribute to tissue segregation during embryonic development.

Mutation = may facilitate the spread of cancer.
Immunoglobulins Family
Stablized by disulfide bonds rather than Ca++

LFA 2 for adehesion to T cells

AUTOIMMUNE DISEASE-

Pemphigus Vulgaris - Antibodies against Desmosomal Cadherins

Mainly Cell-Cell some Cell -ECM

Epithelial Cell: NECTIN
Endothelial Cell: ICAM and VCAM

IgSF bind to Cytoskeleton - actin, aplpha actin, spectrin,
ICAM?
Intercellular Adhesion Molecule

HETEROPHILIC ADHESION
VCAM
Vascular Cell Adhesion Molecule
Tight Junctions
Make sure nothing leaks
1. They are sealing junctions that restrict the movement of proteins in the extracellular medium around epithelia.
2.They contain proteins called Claudins and Occludins.
3. They block the movement of membrane proteins between the apical and basolateral plasma membrane domains of epithelial cells.
4. They are junctions that completely encircle an epithelial cell.
Adherens
Make sure cell stick to one another
Sit on the surface of the cells, making sure they stick
CONNECTING ACTIN of cytoskeleton with CADherins. LOSS of E-Cahereins promotes metastasis.
Cadherens --> AJ's
Sit on the SURFACE of the cells, making sure they stick.
Major protein (component) of Adeherins Junctions. Ca++ dependent. Bind to Beta CATENIN which BIND TO ACTIN.
Also important in tissue specific cell-cell adhesion and cell-sorting
Nectin
Also Participates.
Desomosomes
You have desmosomal casdherens
Strongyly Adhesive. Dynamic and Reversible.
Bind to INTERMEDIATE FILAMENTS

Cell - Cell

1. Actin
2. Microtubles
3. INTERMEDIATE FILAMENTS

Can cause Pemphigus Vulvaris by an autoimmune against desomsomal cadherin.
Non-Healing Blisters.
This is a split between cell-cell.
Hemidesmisomes
Cell - ECM

Integrins interact with laminin and Collagen

Intermediate Filaments.

Can cause Epidermolysis Bullosa - mutation coding for a hemidesmisomal protein, LAMIN 332. Blistering of skin or mucosa in response to minor mechanical trauma or heat.

Can cause Bullous Pemphygoid.

Antibodies attack BP180 (collagen)
This is a split between epidermis and dermis.
Focal Contact
Cell - ECM

Links actin cytoskeleton to ECM.
Have integrins as cell surface protein to do that.
Gap Junctions
Made of 2 connexons
Have Connexin
interCellular communication
Gap Junction Disorder
Oculodentidigital Dysplasia

Caused by a mutation in a gene coding for a connexin.

Gap junction may be less abundant (not trafficked) or abnormal in structure. Could get SYNDACTYLYL
Leukocyte Adhesion
1. Leukocyte free in circulation - non adhesive to endothelial
2. Leukocyte tethered to endothelium and rolling under force of blood flow - selectins -seconds
3. Leukocyte firmly bound to endothelium and migrating -integrins- ICAM
4. Extravasation of leukocytes from blood vessels, JA, PECAM - minutes
5. Leukocyte migrate to source of incection or injury - integrins
B2 Integrin Mutation
Cannot make Pus. Leukocyte Adhesion Deficiency (LAD).
Susceptible to death from overwhelming infection.
Three major platelet adhesion receptors are?
GIIb, GPIa, GPIb
Kinesin
Involved in the movement of vesicles within cells, due to motor proteins carrying those vesicles along MT's.
Actin
Responsible for normal microfilament formation or function.
Dyenins
Are (-) directed MT's proteins.
Myosins
Are (+) directed microfillament proteins.
P-SELECTIN
P-SELECTIN on the endothelial cell surface binds specifically to CARBOHYDRATES groups on proteins on the neutrophil plasma membrane. This promotes the initial weak interaction between the neutrophil and endothelium, which allows rolling due to the fluid flow.
Which of the following statements is most likely to be a common feature of any individual ECM molecule capable of linking adjacent cells to one another?
Has multiple binding sites for cell-surface adhesion molecules.
Integrin
Cell - Cell and Cell - ECM

Bind IgSF, ECM, firbronectin, vWF, collagen.

High affinity for Mn++/and Mg++

Mediate interaction with cytosckeleton, actin and intermediate filaments and transduction signals.

Mutations in integrins can lead to LAD I (no pus)
Selectins
EXCLUSIVELY HETEROPHILIC - CELL-CELL
Ca dep
Bind Carbohydrates on opposite cell

Family

L selectins
E selectins
P selectins

Major role in initiating adhesion of leukocytes and platelets to endothelial cells during inflammation and hemostasis.

L-Selectin - HOMING RECEPTOR
Mediates binding of lymphocytes to HEV in 2condary lymphoid organs (lymph nodes) where they can attack foreign antigens.
TETHRRING AND ROLLING
Connexin
A type of junction that mediates cell-to-cell communication is composed mainly of this protein.
Laminin --> Hemi
Mutation of this matrix protein could lead to a form of Epidermolysis Bullosa because it mediates hemidesmosomal attachement.
Adhesion protein of basement membrane.
Fibronectin
A predictive test for pre-term labour aims to identify this extracellular matrix protein
Selectin
I am a cellular adhesion molecule that is engaged in heterophilic binding only
Hemidesmosome
This adhesion junction is NOT a component of the junctional complex.
Integrin
Binding of platelets to von Willebrand factor is mediated by this type of cell adhesion receptor

SUPER IMPORTANTO TRAP LEUKOCYTES
Fibrin
I form a mesh that binds together various cells and components of the extracellular matrix in order to form an effective blood clot

Protein component of blood clots.
Anoikis
Programmed cell death of cells that detach from the substratum to which they are normally anchored
Paracellular
Zonula Occludens prevents or regulates transport through this channel/space between cells.
Oculodentodigital dysplasia is a genetic disease caused by a mutation in the main protein that makes this type of junction.
Nexus

GAP JUNCTIONS (connexin)

Certain message not sent
I target, and lead to the removal of, the collagenous proteins that help attach intermediate filaments to a cellular adhesion receptor that mediates cell-ECM attachment. My actions result in a skin blistering disease.
ANTIBODY
During leukocyte homing to an infection in the extracellular matrix, this is the process whereby the white blood cells leave the circulation, through the blood vessel wall, to enter the substratum. The process is also called diapedesis.
Extravasation
NectIn is an example of this type of cell adhesion molecule
ImmunoglobulIn
Catenins are located here
Cytoplasm
Defective ADAMTS13 can lead to widespread clumping of these because of formation of large vWF multimers
Platelets
I am one of the main integral membrane proteins that mediate attachment within zonula occludens.
Claudin
After clot formation and the vessel wall has been repaired, I am responsible for dispersing the clot
Plasmin
Maculae adherentes are stabilised by these cytoskeletal filaments
Intermediate
Ehlers-Danlos syndrome is caused by mutations in genes coding for this protein.
Collagen
I am the main adhesion receptor within zonula adherens.
E- cadherin
Fibronectin is found here
Substratum
I am a syndrome that develops when my host�s antibodies attack proteins within the basement membrane of the glomerulus.
Goodpasture
This is the most abundant protein...
Collagen
What secretes and maintains most of the ECM
Fibroblasts
What is BP180 associated with?
Hemidesmosomes
What are the outcomes of Collagen Defects?
1. Osteogenesis Imperfecta

2. Alport Syndrome

3. Ehlers-Danlos Syndrome (cutis hyperelastacia)
Dystrophin
Links the Cytoskeleton to Laminin.
GAGS
Glycosaminoglycans - long carbohydrate chains

LARGE NEGATIVE CHARGE - ABLE TO ATTRACT WATER. osmotically active.
Hyaluronic Acid
Non-sulphated GAGS that helps cartilage resist compression w.out inhibiting flexibility.
Proteoglycans
Sulphated GAG's w. polypeptide.

Osmotically active, attract H20, resist compression.
Marfan Syndrom
Fibrillin mutation.
Most abundant Glycoprotein
Fibronectin
Fibronectin
Adhesion glycoprotein that occurs as fibrils in the ECM and soluble in blood plasma.

attaches cells to other ECM via integrins.
Fibrinogen
Cleaved by thrombin to make fibrin.
Plasminogen
Is converted to Plasmin which then cleaves fibrin to disperse blood clots.
ADAMTS13
Regulate thrombus formation by cleaving vWF multimers.

Mutation: chronic relapsing thrombotic thrombocytopenic purpura (TTP)
ERK
Helps with cell proliferation of cells in ECM. Normally in CYTOPLASM.

If it it escapes it can spread. We don't want it to go to the nucleous.
Anchorage-dependence
exhibited by normal epithelial cells
Cells released from ECM unergo...
Anoikis

*Mammary gland epithelium
*transformed cell can avoid anoikes.
Where are elastic fibers prominent?
Vagina
Anus
Firbonectin and Prego
No increase of Firbronectin, means that she IS NOT GOING OT DELIVER.
Negative is reliable.
Positive not so realiable.
vWD
Genetic Bleeding Disorder
Normal Platelet