19 - Cell junctions

Question 1

What is cell polarity?

Answer 1

Intrinsic asymmetry in cells (shape, structure, organization or cellular components)

Example: epithelial cells, unipolar neurons

Question 2

organization fo the cytoskeleton in maintenance of large-scale polarity

Answer 2

Actin filaments:

• form microvilli whar increase cell surface area for better absorption of nutrients
• circumferential band connecting cells to each other via adherence junctions

microtubules:
- non-centrosomal microtubule network that runds vertically from the top of the cell to the bottom, providing a global coordinate system to direct newly synthetized components to the proper surface

intermediate filaments:
anchored to adhesice structures, connecting cells to the extracellular matrix.

Question 3

Cohesion

Answer 3

mediated by cell junctions, the cytoskeleton and the extracellular matrix

1. epithelial tissues: here the ECM is called the basal lamina, and cells are attached to each other and the basal lamina via junctions that anchor cytoskeletal filaments
2. connective tissues: the ECM bears the mechanical stress, cell-cell contact is rare, cell-matrix junctions are common

Question 4

different types of cell junctions:

Answer 4

tight junction - seals gaps between epithelial cells

adherens junctions - connects actin filament bundle in one cell to that in the next cell (CADHERINS)

desmosome - connects intermediate filaments in one cell to those in the next cell (CADHERINS)

gap junction - allows passage of small water-soluble molecules from cell to cell.

hemidesmosome - anchors intermediate filaments in a cell to the ECM

actin-linked cell-matrix junction - anchors actin filaments in a cell to the ECM

Question 5

cadherins

Answer 5

diverse family of transmembrane proteins only fund in multicellular animals and choangoflagellates

classical cadherins are linked to the actin cytoskeleton, and non-classical ones can be either (i) desmosomal cadherins that are linked to intermediate filaments or (ii) diverse non-classical cadherins

classical cadherins follow the velcro-principle of cell-cell adhesion, a single interaction is weak but multiple ones parallel are strong. The spacing is precicely defined through size of extracellular domain. Binding og Ca++ stiffens the hinge region, turning the string of domains into a rigid, slightly curved rod.

Homophilic binding between cadherins controls tissue segregation; fibroblasts that do not express cadherins do not adhere to each other.

Question 6

adherens junctions

Answer 6

100s ot 1000s of cadherin molecules, often linked to contractile bundles.

Rac dependent:

membrane protrusions initiate cell-cell contact, leading to actin and cadherin recruitment which widens the contact-junction

Rho-dependent: actin remodeling and myosin recruitment expands the adherens junction.

Question 7

DEsmosomes

Answer 7

exist in mature epithelia of vertebrates, structurally similar to adherens junctions but the cadherins are linked to intermediate filaments, and desmosomes provide mechanical strength.

Question 8

tight junctions

Answer 8

tight junctions allow epithelia to serve as selective permeability barriers.

role is to seal and fence: do not allow backflow of f.ex. nutrients that have been taken up by intestine epithelium, and fence by confining the transport proteins to their appropriate domains and act like a diffusion barrier in the plasma membrane

the transmembrane homophilic adhesion proteins claudins and occludins seal of the lumenal space.

Question 9

gap junctions

Answer 9

required for metabolic and electrical coupling of cells. Allow passage of small mlecules and charged ions, for example to synchronixe heart muscle activity.

Two main channel forming proteins: connexins (vertebrates) and innexins

6 connexins form a connexon, and 2 connexons form an intercellular channel. different combinations of connexins/connexons can be created with different properties, for selectiviry/gating mechanism, etc.

Gating mechanisms regulate gap junction permeability

Intercellular Ca++ waves can be propagated by gap functions, the second messenger IP3 can diffuse from one cell to another via gap junctions and trigger release of intracellular Ca++ from SR in the neighboring cell

Question 10

plasmodesmate (intercellular junctions in plants)

Answer 10

only intrercellular junction in plants, connect cells by cylindrical channel, connect smooth ER of two cells for lipid transfer.

Question 11

specialized adhesion mechanisms

Answer 11

selecins:
- Ca-dependent lectin (carb-binding protein)

-heterophilic interaction between P-selecin and P-selectin glycoprotein 1

Ig superfamily members:
-intercellular cell dhesion molecules (ICAMs), vescular CAMs, neural CAMs

Selectins, integrins and ICAMs mediate leukocyte extravasion, allowing them to cross epitheliums.

Question 12

ECM three major classes of macromolecules:

Answer 12

1. Glycosaminoglycans (GAGs), of which there are 4 main groups: hyaluronan, chondroitin sulfate, heparan sulfate , keratan sulfate
2. fibrous proteins like collagens and elastic fibers
3. non-collagen glycoproteins like fibronectin an laminin

+ matrix-associated proteins, like enzymes that modify the matrix.

Question 13

GAGs

Answer 13

Glycosaminoglycan

occupy large amounts of space and form hydrated gels.

GAG composition:
unbranched polysaccharide chains consisting of repeating disaccharide units cosisting of one amino sugar and a uronic acid (usually).
- too stiff to fold, highly hydrophilic and negatively charged, making them attract osmotically active Na+ ions and thus water into the matrix.

HELPS ECM WITHSTAND COMPRESSIVE PRESSURE

Hyaluronan is not a typical GAG, does not have sulfated sugard and are not covalentely linked to a core protein, and they are produced at the cell surface rather than ER + Golgi modification

Question 14

Fibrous proteins

Answer 14

collagen:
- major protein component of ECM
- long and stiff, triple helix
- proline and glycine rich
- can assemble into higher-order structures like fibrils
- fibrils are organized differently in different tissues.

COLLAGEN HELPS ECM RESIST TENSILE FORCES

three types of collagens: - fibrillar (long, ropelike structure, skin and bones)

• fibril-associated (decorate fibril structure for crosslinking/organization, more flexible than fibrillar)
• network-forming collagens

fibronectin is fibrous matrix glycoprotein that guides the organization fo collagen fibrils.

elastin makes up elastic fibers, allow stretch (but has inelastic collagens to limit stretching)

Question 15

complex glycoproteins

Answer 15

fibronectin is a glycoprotein required for cell-matrix interactions.

mediates cell-matric interactions through different domains

major domain is the type III fibronectin repeat domain

RGD sequence!!! important for integrin binding. . RGD = Arg-Gly-Asp

Question 16

the basal lamina

Answer 16

thin, tough, flexible

organized by laminin and anchored to the cell surface through integrins and dystroglycan.

Question 17

degradation of the ECM

Answer 17

Cells must be able to degrade the ECM in order to allow movement, cell division and adaptation

matrix metalloproteases (collagenase) and serine proteases cooperate to degrade matrix proteins

tight regulation either through control of enzyme activity, localization or secretion of inhibitors

Question 18

hemidesmosomes

Answer 18

prominent in epithelia, link laminin outside of cells to keratins within

Question 19

integrins

Answer 19

function both as anchors for matrix and signal translation elements

bind to RGD seqs

most bind to actin cytoskeleton

velcro principle

adhesions can be small and transient or large and stable

convey signals in both directions across the membrane. Integrins switch between inactive and active conformations; regulated by extracellular ligand binding or intracellular adaptor protein binding.