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

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2
Q

Junctional complexes are associated with which cellular domains

  • Apical
  • Basolateral
  • Basal only
  • Lateral only
A

Basolateral

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3
Q

Transtional epithelium is associated with which of the following system?

  • Respiratory
  • Lymphatic
  • Cardiovascular
  • Urniary
A

Urniary

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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

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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

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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

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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
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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)
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9
Q

Fibronectin

A

-a protein made up of two polypeptide chains cross-linked by disulfide bonds

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10
Q

Forms of fibronectin

A
  • Cellular-produced by fibroblasts;part of extracellular matrix
  • Plasma-secreted into bloodstream by hepatocytes
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11
Q

Fibronecting binding sites for what molecules

A
  • heparin
  • integrins
  • collagen
  • Fibrin
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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
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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
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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
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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
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16
Q

Nonclassical cadherins

A
  • Include desmocollins and desmogleins
  • Found in desmosomes(macula adherens)
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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
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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
  • Serve as a major interface between the cadherins that hold adjacent cells together and the actin cytoskeletons of those cells
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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
    1. 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
    1. 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
    1. 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
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
  • 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