What two components make up the basement membrane? Also, what is each component produced by?
1) Basal Lamina -- which is produced by the epithelium.
2) Reticular Lamina -- which is produced by connective tissue
What components make up the basal lamina?
*Laminin *Fibronectin *Type IV collagen >does not form fibrils like type I collagen >type IV collagen is produced by epithelial cells, unlike type I collagen which is secreted by fibroblasts. *Entactin (nidogen) *Proteoglycans
What kind of cells produce type IV collagen, and what type of cells produce type I collagen?
*Type IV -- produced by epithelial cells *Type I -- produced by fibroblasts
Out of all of the components that make up the basal lamina, which component is the major component?
Laminin is the major component of the basal lamina. Laminin consists of three chains: alpha, beta, and gamma, which are disulfide linked polypeptide chains.
What binding sites does laminin have that explains the relationship between laminin and the other components that make up the basal lamina?
Has binding sites for integrins, type IV collagen, entactin, and proteoglycans (e.g: heparin sulfate). Thus, make this connection between the components of the basal lamina and the major component of the basal lamina (laminin).
Is plasma a form of fibronectin? Also, what cell makes plasma?
Yes, plasma is a form of fibronectin. Plasma is secreted into the bloodstream by hepatocytes.
What is fibronectin?
Fibronectin is a protein made up of two polypeptide chains cross-linked by disulfide bonds.
What does fibronectin have binding sites for?
*Heparin (proteoglycan) *Integrins *collagen *Fibrin
What type of cell produces cellular fibronectin?
Cellular fibronectin is produced by fibroblasts; which is part of the extracellular matrix.
Objective 2 Describe the major kinds of cell adhesion molecules (CAMs) and their role in forming cell-to-cell complexes.
Objective 1 Describe the structure and components of the basement membrane.
Which two CAMs are considered calcium dependent and which two are calcium independent?
Calcium Dependent --> Cadherins and Selectins Calcium Independent --> Integrins and Immunoglobulin superfamily molecules
What family of CAMs do occludens and desmosomes fall under? Also, is this class calcium dependent?
Cadherins -- YES, calcium dependent.
What family of CAMs do hemidesmosomes fall into? Is this class calcium dependent?
Integrins and NO, not calcium dependent.
What ligands do selectins recognize?
What ligands do the Ig Superfamily recognize?
Where are E-cadherins, N-cadherins, and P-cadherins found in the body?
E-cadherins --> found in epithelial tissues N-cadherins --> found in nerve cells P-cadherins --> found in the placenta
What amino acid sequence does E-cadherins form dimers by?
Calcium ions bind to four extracellular domains and facilitate ______?
What are catenins?
Small proteins that link the cytoplasmic end of a cadherin with cytoplasmic actin. ***Note that catenins serve as a major interface between the cadherins that hold adjacent cells together and the actin cytoskeletons of those cells***
What are the three forms of catenins?
>alpha -- binds directly to cytoplasmic actin >beta and gamma -- attached to cytoplasmic end of a cadherina, beta may also serve as a transcription cofactor, and beta is also attached to alpha catenin.
Selectins are involved in the movement from blood to tissues (extravasation) for which type of cells?
What are the 3 types of listed selectins associated with? *P-selectins *E-selectins L-selectins
E-selectins --> associated with activated endothelial cells P-selectins --> associated with platelets L-selectins --> associated with leukocytes
What are integrins? How many subunits make up an integrin?
Integrins are glycoproteins that are mainly involved in cell-extracellular matrix interactions. Each integrin consists of 1 alpha subunit (17 kinds) and 1 beta subunit (8 kinds).
Do integrins bind to both the extracellular matrix and the cytoskeleton?
YES, with the extracellular domains binding to molecules such as fibronectin and laminin through an RGD (Arg-Gly-Asp) interaction sequence.
Give an example of an intracellular tonofilament that integrins link with to connect the basal domains of cells to the extracellular matrix. Also, in what type of stable junction is this found?
Keratin is the tonofilament and this action is found in the hemidesmosome.
True or False: N-CAMs are neural adhesion molecules that mediate only heterophilic interactions?
False --> They mediate both homophilic and heterophilic interactions.
What do I-CAM-1 facilitate?
They facilitate transendothelial migration of Leukocytes.
Objective 3 Be able to describe the types of junctional complexes and relate them to the cohesive nature of epithelia.
What are the 3 categories of junctional complexes?
*Adherens *Occludens *Gap Junctions
What are the 2 main functions of the occluden junctional complexes?
1) to prevent paracellular transport 2) maintain concentration differences
What are adherens? Also, what portion of the cell are they found?
Adherens are molecular complexes that anchor cells together and reinforce the physcial integrity of tissues and the cells that make up the tissues.
Adherens can be found on the basolateral surfaces of epithelial cells.
What are occludens (tight junctions)?
Occludens are molecular complexes that establish an impermeable barrier between adjacent cells, especially epithelial cells, that prevents paracellular transport and maintains concentration differences between the environments on either side of the epithelial sheets.
What are gap junctions?
Gap junctions are composed of molecular pores that enable cells to rapidly exchange ions and small molecules that help coordinate activities among the cells that make up the tissue.
True or False:
Zonula Junctions can be either of the adherens or occludens variety?
True or False:
Macular Junctions can be from either of the adherens or occludens variety.
False, they are of the adherens variety and are often referred to as desmosomes or hemidesmosomes.
Between the desmosome and hemidesmosome, which is associated with the lateral domains of epithelial cells and which is associated with the basal domain of epithelial cells?
desmosomes--> associated with the lateral domains of epithelial cells.
hemidesmosomes--> associated with the basal domain of epithelial cells.
Between the Zonula or Macula Junction, which one is associated with intracellular actin and which one is associated with intracellular intermediate filaments (tonofilaments)?
Zonula --> associated with intracellular actin
Macula --> associated with intracellular intermediate filaments (tonofilaments)
What are the two cadherin proteins that mediate the interaction between zonula adherens with actin microfilaments and macula adherens with intermediate filaments (tonofilaments)?
True or False:
The cadherin proteins are anchored to cytoplasmic plaques containing desmoplakin and plakoglobin?
What is the hemidesmosomes function?
Hemidesmosomes are anchoring junctions that anchor the basal domain of the epithelial cell to the basal lamina.
What is pemphigus foliaceus?
Pemphigus foliaceus is an autoantibody-mediated blistering disease in which antibodies against desmoglein 1 cause a loss of adhesion of keratinocytes in the superficial layers of the epidermis.
In which layer of the epidermis is the desmoglein 1 predominatly found that is involved in the blistering disease, Pemphigus foliaceus?
Just above the stratum spinosum in the stratum granulosum.
True or False:
Occluding junctions (zonula occludens) provide a barrier against the paracellular transport pathway whereby solutes and fluids are transported from one side of an epithelial barrier to the opposite side by passing between the cells?