how many types of epithelial junctions are there? where are they located?
5 total. 4 in lateral domain. 1 in basal domain
what are the two general roles of epithelial junctions
cellular adhesion, cellular communication
what are the 4 major families of cell adhesion molecules (CAMs)
cadherins, integrins, immunoglobulin super family, selectins
which CAMs are responsible for epithelial cell jxns?
cadherins and integrins
which CAMs play a role in inflammation?
IGSF and selectins
what is the general structure of cadherins and integrins
transmembrane proteins with extracellular binding domains
Cadherin: type seen in epithelial cell? Calcium? Interactions in the intracellular domain? role?cancer?
E- cadherin seen in epithelial cells Ca dependent extracelular domain (CA dependent ADHERINs) associated with catenins that link the adherin to the actin cytoskeleton important in cell-cell connections; cell recognition, tumor suppresssion cancer cells lose cadherin molecules and are able to metastasize
Intergrins: strucutre? Calcium? role 3?
heterodimer: alpha and beta chains calcium independent cell-cell, cell-ECM binding, facilitates cell movement in ECM
what are the four types of cell jxns found in the lateral domain of epithelial cells?
zonula occludens (tight jxn), zonula adherens (intermediate jxns), macula adherens (desmosomes), gap jxn
what is the general location of zona occludens?
this is the most apical jxn
what is the general location of zona adherens
just beneath the Zona occludens
where are macula adherens found on the lateral domain of epithelial cells?
erratically. desmosomes are sometimes termed "spot welds". below zona adherens (more towards basal surface)
what is the role of gap junctions?
permit direct passage of signaling molecules from one cell to another
what is the role of Zonula occludens?
tight jxns. forms a barrier that prevents paracellular transport (transport between cells). separates apical domain from the basal and lateral domain
what are two proteins associated with zonula occludens?
occludin and claudin
what is the function of zonula adherens?
intermediate junctions. anchor cells to each other through actin filaments within the cell attached to cadherin and catenins
what is the funciton of macula adherens?
desmosomes: spot welds between epithelial cells that resist shear force.
what proteins are associated with macula adherens? 4
desmoglein, desmocolin (cadherin), desmoplakin, plakoglobin
given the fxn of macula adherins, where would we expect to see them in the most abundance?
stratified squamous epithelium (skin's epidermis) where cells must resist a lot of friction
gap junctions are made of ____ which form____
connexin which forms connexon
what is the overall function of the basal domain
anchors epithelium to the Basement membrane
what are the two regions of the basement membrane
basal lamina (more superficial; interfaces with connective tissue and epithelial cells) and reticular lamina (more deep)
what is the clinical significance of the basal lamina
penetration of the basal lamina indiacates a tumor is undergoing malignant progression and is capable of metastasis
what is the role of focal adhesions? 2
link network of cytoplasmic actin filaments to basal lamina proteins (attach cell to ECM), signal transduction from ECM to cell
focal adhesions are made of ____ and bind to ___3__ in the basal lamina
integrins. fibronectin, collagen, laminin
what is the role of hemidesmosomes?
anchor the basal plasma membrane to the basal lamina
what are the 2 important structures you should associate with hemidesmosomes
BP230, basement membrane
Pemphigus vulgaris: what type of jxn is affected? how? which domains are lost? where/what type of blister?
desmosomes are lost: cell attachement to each other are lost, but basal domain remains. body creates antibodies against desmogleins 1 and 3. flaccid blisters occur in the epidermis
what is Nikolsky's sign?
a test where a pencil eraser is twirled on the skin, if a blister develops it is a postive test for a blistering skin condition
Bulous Pemphigoid: what type of jxn affected? how? which domains are lost? what type of blister?
body produces antibodies against BP230 and destroy hemidesmosomes. cells lose basal domain connection but keep lateral domain. tense blister
Blisters: what are they, where do they form? what types?
Clear area filled with leukocytes and fibrin, form between intact epidermis and the dermis. Flaccid=easy to rupture, Tense=difficult to rupture
what causes dystrophic epidermolysis bullosa? why is this a problem?
inherited defect in collagen VII. collagen VII plays a role in holding the BM to the underlying connective tissue. epidermis with attached BM comes off surface. Epidermis+BM shears right off (loss of dermal-epidermal jxn).
does dystrophic epidermolysis bullosa impact anything other than skin? why?
yes. Collagen VII is important in stratified squamous epithelium which is also seen in the esophagus.
Dystrophic Epidermolysis Bullosa