Cell adhesion Meolcuels and Junctional Complexes Flashcards
1
Q
Simple non ciliated columnar epithelium is most likely to be found associated with which of hte following?
- urniary tract
- respiratory tract
- integument
- digestive tract
A
digetive tract
2
Q
Junctional complexes are associated with which cellular domains
- Apical
- Basolateral
- Basal only
- Lateral only
A
Basolateral
3
Q
Transtional epithelium is associated with which of the following system?
- Respiratory
- Lymphatic
- Cardiovascular
- Urniary
A
Urniary
4
Q
Although not common,stratified cuboidal epithelium may be found in which of the following areas?
- Vaginal epithelium
- Part of the male urethra
- urniary bladder
- kidney tubuels
A
Male urethra
5
Q
Lightly keratinizied stratified squamos epithelium is chareceristic of which of the following locations?
- Vaginal Epithelium
- Part of hte male urethra
- Urniary bladder
- kidney tubuels
A
Vaginal epithelium
6
Q
Charecteristics of the basement membrane
A
- Basement membrane separates an epithelial layer from its connective tissue support
- Basement membrane is approxmimately 50-80nm thick
- Basement membrne consists of two components
–basal lamin-produced by the epithelium
–Reticular lamina produced by the connective tissue
-not a cellular membrane PAS+ can really see basement mebrane
7
Q
Components of Basal Lamina
A
- Laminin -Fibronectin-
- Type IV collagen
– type IV collaen coes not form fibirls like type I collagen
– Type IV collagen is produced by epithelial cells ,unlike type I collagen which is secreted by fibroblasts
- Entactin(nidogen)
- Proteoglycans
8
Q
Laminin:charecteristics
A
- This is the major component of the basal lamina; it consists of three chains:a,b,y
- Laminin has binding sites for integrins, type Iv collagen, entactin and proteoglycans(IE , heptran sulfate)
9
Q
Fibronectin
A
-a protein made up of two polypeptide chains cross-linked by disulfide bonds
10
Q
Forms of fibronectin
A
- Cellular-produced by fibroblasts;part of extracellular matrix
- Plasma-secreted into bloodstream by hepatocytes
11
Q
Fibronecting binding sites for what molecules
A
- heparin
- integrins
- collagen
- Fibrin
12
Q
A
- Laminin is hte major component of hte basal lamina
- consists of three disulfide linked polypeptide chains designated a, b,y chains
- Varients for each chain give rise to several laminin isoforms with different strucutre and fuction
- Have binding sites for cell surface receptors(integrins),type IV collagen, and other adhesioin proteins(ex. nidogen aka entactin)
- Laminin monomers self-associate to form a network that is part of the basal lamina
13
Q
A
Fibronectin
- A glycoprotein formed by two identical chains joined by disulfide linkages close to the C-terminal
- two forms
- Plasma fibronectin-produced by hepatocytes and secreted into the bloodstream
- Cellular fibronectin-produced by fibroblasts ,forms part of the extracellular matrix
- Has binding sites for integrins, collagens , heparan sulfate and fibrin
14
Q
Cell Adhesion Molecules(CAMs)
A
- Depending on the need for calcium in their interactions with other molecules , cell adhesion molecules are divided into two groups
- Calcium dependent
- Cadherins
- Selectins
- Calcium indepndent
- Integrins
- Immunoglobulin superfamily molecules
- Calcium dependent
15
Q
Classical Cadherins
A
- Major components in calcium mediated adherens junctions
- TYpically form cis and trans homophilic dimers
- include:
- E-cadherins:found in epithelial tissues
- N-Cadherins:found in nerve cells
- P-cadherins: found in the placenta
16
Q
Nonclassical cadherins
A
- Include desmocollins and desmogleins
- Found in desmosomes(macula adherens)
17
Q
E-Cadherins
A
- The most common type of cadherins
- Form dimers via a HVA binding face(Histidine-valine-alanine sequence)
- Found at tip of extracellular end of cadherin molecule
- calcium ion binds to four extracellular domains and facilitate cis-homophilic dimers
- Loss of e-cadherins is associated with invasive behaviors of tumor cells
- Cadherin molecules pass through the cell membrane and will have an intracellular and extracellular component
- Need to link cell to basement membrane and see other integrins linking together the cytoskeleton with other proteins
18
Q
Catenins
A
- Small proteins that link the cytoplasmi end of a cadherin with cytoplasmi action
- three forms:
- B and y/plakogolobin catenins:
- Attached to cytoplasmic end of a cadherin
- Beta may also serve as a transcription cofactor
- Beta is also attached to alpha catenin
- insdie the cell
- a catenin
- Binds directly to cytoplasmic actin
- B and y/plakogolobin catenins:
- Serve as a major interface between the cadherins that hold adjacent cells together and the actin cytoskeletons of those cells
19
Q
Selectins
A
- Selectins bind to carbohydrates;therefore , they belong to the lectin group
- The binding site for carbohydrates is located at the carbohydrate-recognition domain(CRD) at the extracellular end of the selectin
- Calcium binding sites are also found near the CRD and calcium is required for the binding activity
- Selectins are invovled in the movement of leukocytes from blood to tissues(extravasation)
- Extravasation-moving out of the blood cells
20
Q
Selectins and types
A
- Selectins have three extracellular domains
- A carbohydrate recognition domain(CRD) specific for particular sugar(galactose, mannose,N-acetylgucosamine, and others)
- A domain homologous to a repeat found in epidermal growth factor(EGF-like)
- Many consensus repeats found in complement regulatory proteins
- 3 major types of selectins:
- L-selectin- carried by lymphocytes and with binding affinity to sulfated carbohydrates
- E-selectin-expressed by activated endothelial cells
- P-selectin-expressed by platelets and activated endothelial cells
- Selectins, together with integrins and intercellular cell adhesion molecules(ICAMs) play a siginifcant role in inflammation and in the periodic migration of lymphocytes from the circulation into lymphoid organs(homing)
21
Q
Integrins
A
- Glycoproteins that are mainly involved in cell extracellular matrix interactions
- bind to both the extracellular matrix and to the cytoskeleton
- Consist of two subunits:
- Each integrin consists of one alpha subunit(17 kinds) and one beta subunit(8 kinds)
- Extracellular domains of integrins bind to molecules in the extracellular matrix such as fibronectin and laminin
- In hemidesmosomes , integrins link the basal domains of cells to the extracellular matrix via the intracellular tonofilaments(intermediate filaments such as keratin)
- intermediate filaments are slightly larger in diamter then actin
22
Q
What sequence in fibronectin and laminin do integrins interact with?
A
- Interact with RGD(Arg-Gly-Asp)
23
Q
Laminin and fibronectin in the basement membrane interact with what?
A
- collagen
- heparan sulfate proteoglycans
- entactin(nidogen)
24
Q
How do integrins differ from other cell adhesion proteins
A
- Consist of two subunits
- Have a dual function
- Bind to the extracellular matrix
- Bind to the internal cytoskeleton
- a subunit of an integrin has two chains linked by a disulfide linkage and a globular head with binding sites for divalent cations
- B subunit has two significant charecteristics
- Extracellular chain contains repeating cysteine-rich regions
- Intracellular portion interacts with actin filaments through three connecting proteins:
- Talin
- Vinculin
- a-actinin
25
Q
Neutrophil Homing
A
- 1.Leukocytes(neutrophils) in circulation resist shear forces to slow down along the vascular endothelium
- Loose adhesion to the endothelium under conditions of slow flow causes the leukocytes to roll.
* Selectins present on the endothelial cell surface bind to carbohydrate ligands on the leukocyte surface
- Loose adhesion to the endothelium under conditions of slow flow causes the leukocytes to roll.
- Integrin receeptors for endothelial ICAM-1 and ICAM-1 ligands are rapidly activated on the leukocyte surface druing rolling
* Chemical mediators in the sites of inflammation stimulate the activation of integrins B1 and B2.
* Integrins strengthen leukocyte binding to endothelial cell surfaces
- Integrin receeptors for endothelial ICAM-1 and ICAM-1 ligands are rapidly activated on the leukocyte surface druing rolling
- Transendothelial migration is mediated by integrins interacting with ligands on endothelial cell surfaces. F-actin dynamics participate in this process
26
Q
Immunoglobulin Superfamily
A
- Members of this family possess an extracellular segment with one or more folded domains charecterisitc of immunoglobings
- Members of the IG-superfamily
- N-CAM-are neural adhesion molecuels
- they mediate both homophilic and heterophilic interactions
- I-CAM-1 and I-CAM-2:
- I-CAM-1 facilitates transendothelial migration of leukocytes
- N-CAM-are neural adhesion molecuels
27
Q
Adherens
A
- These are molecular complexes that anchor cells together and reinforce the physical integrity of tissues and the cells that make up the tissues
- Can be found on the basolateral surface of epithelial cells
- Most reponsible to holding together cells , particular epithelial cells
28
Q
Occludens
A
- Molecular compelxes 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 hte epithelial sheets
- prevent paracellular transport, prevent molecules from slipping by the cell surveillance and linking between cells
29
Q
Gap Junctions
A
- These are composed of molecular pores that enable cells to rapidly exchagne ions and small molecules that help coordinates activities among the cells that make up the tissue
- Can help spread signal molecuels to cell to cell
30
Q
Zonula
A
- This can be either of the adherens or occludens variety
- Zonula complexes travel all the way around the circumference of the cell and link all neighboring cells to the central cell. They are sometiems referred to as belt-like compelxes
- Associated with intracellular actin
31
Q
Macula
A
- A spot or snap like junction
- They are of the adherens variety and are often referred to as desmosomes (associated with the lateral domains of epithelia cells) or hemidesmosomes(associated with the basal domain of epithelial cells)
- The are associated with intracellular intermediate filaments(tonofilaments)
*
32
Q
What type of proteins fill Adherens
A
- These are anchoring junctions charecterized by intercellular spaces which are filled with cadherin proteins
- Desmogleins
- Desmoglein 1 and 2 are found in the epidermis
- autoantibodies to the desmoglein 1 result in pemphigus foliaceus
- Desmocollins
- Desmogleins
- Cadherin proteins are anchored to cytoplasmic plaques
- Desmoplakin
- Plakoglobin
- If you have autoantibodies producd against desmoglein 1
- Predominateed in the above status spinosum in straited epithelial cells
33
Q
Adherens junctional compelxes
A
- Zonula adherenes are associated with actin microfilaments
- Macula adeheres are associated with intermediate filaments(tonofilaments)
- These associations are mediated by interactions with cadherins:
- Desmocollins
- Desmogleins
34
Q
A
Desmosomes in stratified Squamos Epithelium
35
Q
Hemidesmosomes
A
- Hemidesmosomes are anchoring junctions that anchor the basal domain of the epithelial cell to the basla lamina
- A hemidesmosome conssits of:
- Cytoplasmic palte associated with intermediate filaments such as keratin
- A membrane plaque linking the hemidesmosome to the basal lamina via anchroing filaments(laminin 5) and integrins(integrina6B4
- Note that at one time,hemidesmosomes were thought to be half demosomes, with the desmosome associated with the epithelial cell
36
Q
Zonula Occludens
A
- Zonula occludens(tight junction) is a belt-like occluding junction
- Occluding junctions provide a barrier against the paracellular transport pathway whereby solutes and fluids are transported from one sdie of an epithelial barrier to the opposite side by passing between the cells
- Claudins and occludins are transmembrane proteins associated with unctional complex and are responsible for the occlusive properites of the tight junction;they attach intracelluarly to zonula occludens proteins ZO-2 and ZO-3
37
Q
Transmembrane proteins include jucntional adhesion molecules(JAMs) and Nectin related to Zonula Occludens
A
- Both JAMs and nectin are members of the immunoglobulin superfamily. They are stabilized by disulfide bonds and form cis-homodimers that facilitae cell adhesion
- Nectin is associated with an intracellular molecule, afadin
- JAMs are associated intracellularly with both afadin and with ZO-1
- The zonula occludens proteins and afadin facilitate interaction with the intracellular actin filaments
38
Q
Focal Adhesions
A
- Spots tah anchor the cell to the extracellular matrix via integrins
- Differ from desmosomes in that the intracellular attachment is not to tonofilaments such as keratin but to actin filaments via connecting proteins
- Focal adhesions may be very stable interactions invovled in tissue integrity or may turn over rapidly as cells move
- Extracellular portions of the integrins may be folded clsoe to the plasma membrane and unattached to the ECM
- Cytosolic signals may cause the integrin heads to unfold and attach to ECM components such as fibronectin or laminin
- can be ery stable or turn over very rapidly which allow cells to make or break junctions very easily
- can be extended or folded
39
Q
Gap Junctions
A
- Gap junction is a communicating junction that allows cell to directly communicate
- Gap junctions are composed of connexons:
- Each connexon consists of 6 connexins ,forming a hexagonal strucutre with a hollow cneter
- Connexons facilitate movement of molecules up to 1.2nm in diameter
- Connexons are often clustured into patches
- Connexons going from cytoplasm to cytoplasmand faciliates flow of information from one cell to the other
40
Q
When do Gap junctions close?
A
- Close when calcium ion concentrations are high
- Gap junctions are reponsible for chemical and electrical coupling
- Each connexon consists of 6 connexins, forming a hexagonal strucuture with a hollow center
- Related pathologies include:
- Charcot-Marie-Tooth neuropathy
- Congenital cataracts
41
Q
Basal lamina is associated with which type of collagen
A
Type IV
42
Q
Which of the following types of cell adhesion molecule is associated with zonula occludens and desmosomes?
A
Cadherins
43
Q
Desmocollings and Desmogleins belong to which of the following groups of Cell adhesion molecules(CAM)
A
Cadherins
44
Q
Extracellular domains of which of the following bind to molecules in the extracelular matrix such as fibronectin and laminin?
A
Integrins
45
Q
Which of the following are molecular complexes that anchor cells togehter and reinforce the physcial integrity of tissues and the cells that make up the tissues?
A
Zonula adherens
46
Q
Which of the following are molecular complexes that primarly serve to prevent paracellular transport?
A
Zonula Occludens
