BIO230 - Lecture 3 - Cell adhesion

cell adhesion

-how cells stick together

what is essential for multicellular organisms?

-cell cohesion

mechanical stresses

-are transmitted from cell to cell by cytoskeletal filaments anchored to cell-matrix and cell-cell adhesion sites

ECM

-directly bears mechanical stresses of tension and compression

basal lamina

-specialized ECM

epithelial tissue

-cells directly connected to each other with minimal extracellular matrix

-adhesion to the basal lamina ECM (role of cell-matrix junctions in this tissue)

connective tissue

-cells dispersed through extracellular matrix

-cell interaction with the ECM and cell movement (role of cell-matrix junctions in this tissue)

what type of tissues do many animal cells have?

-either connective or epithelial tissue

what do epithelial and connective tissues support?

-they support the animal body plan

epithelial cells

-lines surfaces, cavities, and organs

-surround and define organs

-are polarized (ends are different)

-each cell surface must be different to perform different functions → these cell surfaces define the inside vs. outside of the organism or tissue

what are some examples of epithelial cells lining surfaces, cavities, and organs?

• protective epithelial cell layers on the surface of the organism (skin)

• absorptive epithelial cells lining a cavity of the organism (digestive tract)

what does the epithelial structure and function require?

-it requires junctional complexes

what is junctional complex order of the mature epithelial structure?

APICAL: (facing outside) **these 4 are lateral junctions

• tight junctions

• adherens junctions

• desmosome

• gap junction

BASAL: (facing basal lamina)

• hemidesmosome

• actin-linked cell matrix junction

cell-cell anchoring junctions

-stick 2 (cells) junctions together

-usually mediated by cadherin family members

what are the 2 types of cell-cell anchoring junctions?

1. adherens junctions

2. desmosome

what are 3 components of the junctional complexes?

1. tight junctions

2. adherens junction

3. desmosome

cell-matrix anchoring junctions

-sticking 2 cells together

-usually mediated by integrins

what are the 2 types of cell-matrix anchoring junction?

1. hemidesmosome

2. actin-linked cell-matrix junction

tight junctions

-seals gap between epithelial cells → block junctions

-forming sealing strands

-limit diffusion in the extracellular space → since they block things

-prevent membrane proteins from moving between the apical and basolateral domains

-regulate what enters an organism

-forms apical to the adherens junctions

adherens junction

-connects actin filament bundle in one cell with that in the next cell → all along the region of 2 cells

-forms adhesion belt

-these form first out of all the other junctions

-provide polarity cues to define apical from basolateral domains

desmosome

-connects intermediate filaments in one cell to those in the next cell in one spot

gap junctions

-allows the passage of small water-soluble molecules form cell-cell

-in the category of channel-forming junction

hemidesmosome

-anchors intermediate filaments in cell to ECM

actin-linked cell-matrix junction

-anchors actin filaments in cell to ECM

what can link to the cytoskeleton?

-junctional complexes can link to the cytoskeleton (may be actin or intermediate filaments)

cadherins

-are transmembrane proteins expressed by both cells

-they mediate cell-cell connections at adherens junctions

-interact homophilic interactions of their extracellular domains

-intracellular domains indirectly interact with actin filaments

-form homophilic interactions with their extracellular domains to directly link adjacent cells → these interactions indirectly link the actin cytoskeleton between adjacent cells in epithelial tissues

-many of these interact in patches to form a strong adhesion belt

-cells express different types of this to establish new interactions and ensure neural tube closure

what do cadherins extracellular domains directly interact with eachother require?

-this interaction requires Ca2+ → to stick to one another (it keeps the hinge region rigid)

homophilic

-only the same types stick to one another

what are the sorted cell groups based on homophilic cadherin interactions?

homophilic interactions:

→ from between cells expressing E-cadherins

→ from between cells expressing N-cadherins

no heterophilic interactions:

→ occurs between E-cadherins and N-cadherins

what is the result of sorting cells expressing different cadherins?

-the result is cells expressing different cadherins sort into 2 separate groups that do not interact

adhesion belt

-all along the region of 2 cells

-formed by many cadherins interacting in patches

-mediates morphogenesis

-its contractions pull cells to form a tube

morphogenesis

-to generate tissue shapes

what is essential for embryo development and morphogenesis?

-cell adhesions is essential

what most closely resembles adherens junctions mutations in the outer epithelium of Drosophila embryos?

-Ca2+ removal at the out epithelium

what defines domains of cells?

-tight junctions do

where does the apical domain face?

-it faces the surface, cavity, or organ

where does the basal domain face?

-it faces the inside of the body

what are the basal and lateral domains often grouped as?

-they are grouped as the basolateral domain

what are domains maintained by?

-domains are maintained by tight junctions

what forms tight junctions?

-occludins and claudins form these

occludins and claudins

-4 pass transmembrane proteins

-form homophilic interactions with their extracellular domains to directly link adjacent cells

-form functional tight junctions

what type of interactions do transmembrane occludins and claudins form?

-they form homophilic interactions with their extracellular domains to directly link adjacent cells

what do many rows of occludins and claudins form?

-they form a functional tight junction

can membrane proteins diffuse in the plasma membrane?

-yes they can diffuse in the plasma membrane

what do tight junctions do when it comes to glucose transport into the cell?

-they stop anything from directly diffusing from the gut lumen into connective tissue & blood (proteins are kept on proper side) and they keep the correct transporters in their correct domains of the cell

Na+-driven glucose transporter

-uses Na+ from high to low conc. to move glucose from low to high conc.

what is the Na+ driven glucose transporters role in glucose transport into the epithelial cell?

-its role is to move glucose into the epithelial cell on the apical domain

what is the role of the passive glucose transporter in glucose transport into the epithelial cell?

-its role is to allow glucose to diffuse out of the epithelial cell into the connective tissue/blood, since it is located in the basolateral domain

-moves glucose passively from high to low conc.

integrin heterodimers

-mediate cell-to-cell-matrix junctions

-directly bind extracellular matrix proteins

-have a transmembrane domain

-indirectly interact with actin filaments

-can provide the adhesion necessary for cell migration through actin-integrin-ECM interactions

what can establish cell cohesion?

-polarity cues can establish this

cell cohesion

-cells working together

polarity cues

-helps the cells establish their ability to work together

what are the 3 polarity cues that adherens junctions use to define apical from basolateral domains?

1. PAR

2. Crumbs

3. Scribble

PAR

-polarity cue

-for apical domain

-works with Crumbs

-activated by adherens junction

-inhibits scribble from the apical side

Crumbs

-polarity cue

-activated by adherens junctions

-works with PAR

-for apical domain

-also indirectly (through PAR) inhibits scribble from the apical side

scribble

-for the basolateral domain

-polarity cue

-activated by adherens junction

-inhibits PAR from the basolateral side

what can generate subsequent patterns?

-an initial landmark can generate subsequent patterns

primary landmark (some polarity) → subsequent elaboration (even more polarity)

**dots can represent => molecules in a cell, cells in a tissue

landmark

-can be a structure, a protein, a signal, or a process

-some molecules move toward it and some molecules move away from it, creating polarity

what can polarize cell behaviour?

-extracellular signals

how can cell polarity be established?

-cell polarity can be established by external or internal signals

what is an example of cell polarity being established by external or internal signals?

fertilization: (development)

• initial polarity signal was external → sperm entry

• asymmetric cell division can unevenly distribute internal polarity cues between child cells

**in development very very often there's some kind of landmark and then there's elaboration of this polarity

what can an occludin mutation in intestinal epithelial cells directly affect?

-an occludin mutation in intestinal epithelial cell will directly affect glucose transport → since this mutation affects tight junctions, which normally block things)

what are the 3 key components of cell polarity that define a functional epithelium?

1. intracellular trafficking

2. cytoskeleton organization

3. cell cohesion

what does a functional epithelium define?

-it defines organs and organisms