Lecture 16. Cell junctions, cell adhesion and extracellular matrix

1. Cell junctions

• tight junctions

• adherens junctions

• desmosomes

What can’t pass through tight junctions?

water molecules

What do tight junctions do?

They seal the gaps between epithelial cells

What do adherens junctions connect?

connect actin filament bundles in one cell with those in the next cell

• connect the cytoskeleton of cells to each other or to the extracellular matrix

What do desmosomes connect?

They connect intermediate filaments in one cell to those in the next cell

What do gap junctions allow?

Allow the passage of small water-soluble molecules from cell to cell

• act like channels

What do tight junctions form?

Barriers between the apical and basolateral domains

How are tight junctions sealed?

By claudins and occludins

• transmembrane proteins

What are examples of cell-cell anchoring junctions?

• adherens junctions

  • desmosomes

What do adherens junctions form?

They form adhesion belts between epithelial cells

What do cadherins protein mediate?

They mediatet cell adhesion to the adherens junction

What are cadherins proteins?

Are calcium dependent homotypic cell adhesion proteins

• without calcium binding is weak

Where do cadherins bind?

They bind to the actin cytoskeleton through anchor proteins called catenins

What is special about cadherins?

They tend to self-aggregate and have affinity for eachother (E vs. N)

What’s an important example of cadherins?

They play an important role in neural tube development

• invagination

What is an E-cadherin?

Epithelial cadherin

What is N-cadherin?

Neural cadherin

What happens during development in cells?

They segregate from one another depending on the cadherins they express

Pop Quiz

Cells expressing either N-cad (A), high levels of E-cad (B), or low levels of

E-cad (C) have sorted themselves out on a substratum as shown below.

A, C, B

• N is a seperate group (grey)

• C is low E so it’s “hiding”

  • and high E is on the outside, still interacting with low E

What do desmosomes serve as?

Serve as anchoring sites for intermediate filaments

• are connected internally to intermediate filament in cytoskeleton

What serve as the transmembrane recepetors in Desmosomes?

Desmoglein and desmocollin

• form a heterodimer

• are cadherin-family members

What serve as the intracellular anchoring proteins in desmosomes?

Plakoglobin and desmoplakin

What would result if there was a mutation in the anchoring proteins (plakoglobin & desmoplakin)

Prevents binding of desmosomes to intermediate filaments

What diseases result from desmosomes?

Skin diseases where antibodies are made against their own desmosomal proteins, result in severe blistering

What are Cell-ECM anchoring junctions?

Focal adhesions and hemi-desmosomes

What is a focal adhesion?

actin-linked cell-matrix adhesion anchors actin filaments in cell to ECM

What are hemidesmosomes?

Hemidesmosomes anchor intermediate filaments in a cell to the ECM

What makes up the focal adhesion structure?

Integrins and Vinculin

What are integrins?

they’re the receptors that cluster at focal adhesions. Bind to many ECM components including collagens and laminins

• binds to many things to ensure it’s tightly bound to basal lamina

What is Vinculin?

Vinculin marks focal adherins where bundles of actin filaments terminate at the plasma membrane, connecting receptors that bind the ECM

• adaptor proteins bind to actin

  • are inside the cell

Why are integrins important

They’re the major receptor for the ECMW

What makes up a transmembrane heterodimer?

alpha and beta subunits that are held together by noncovalent bonds

• 9 types of beta subunits

  • 24 types of alpha subunits

How are hemi desmosomes different or similar to focal adhesions?

• Similar: Integrins act as the transmembrane receptor and the anchor is to the ECM

  • difference: the intracellular attachment is to intermediate filaments (similar to desmosomes)

What is selectin?

a protein that’s highly expressed in endothelial cells (cell wall)

What do selectins do?

They mediate transient cell-cell adhesion in the bloodstream

• mediate heterotypic binding

  • they bind to carbohydrates (sugars/lectins) that are attached to the surface of cells

How do selectins and integrins work together?

They let white blood cells leave the bloodstream and enter tissues

When there is weak adhesion and rolling what is present?

Selectin

When there is strong adhesion and emigration what is present?

Integrin

2. Extracellular matrix (ECM)

How is connective tissue important?

connective tissue under the epithelium contains a variety of ECM components, many of which are made by fibroblasts

What are Glycosaminoglycans (GAGs)?

an ECM component

• polysaccharide

• unbranched polysaccharide chains composed of a repeating disaccharide unit

• are highly negatively charged, attract Na+ ions

• occupy a huge amount of space and form hydrated gel

What are proteoglycans?

An ECM component

• GAGs that are linked to a protein backbone

• an ex. is aggrecan found in cartilage

What is collagen?

An ECM component

• synthesized by fibroblasts

What is the structure of collagen?

• an alpha chain

• 3 alpha chains wrap around each other to form a triple-stranded helical rod

Where can the different types of collagen be found?

Bone, cartilage, skin, and blood vessels

What can happen if there’s a collagen gene mutation?

Weak bones, easier to fracture, joint or bone deformaties

What is basal lamina?

An ECM component

• underlies all epithelial sheets

What does basal lamina contain?

laminin, perlecan, nidogen, and type 4 collagen

3. Case study - role of beta 4 integrin

What is beta 4 required for ?

Hemidesmosome formation

• skin issues/blisters