Block 4 - Breslin - Cell Junctions and Cell Adhesion

Adhesion helps with sticking but can also help with

cell trafficking and migration

Functions of cell-cell junctions and adhesions

tissue formation, development, migration, ect.

Ways in which cells attach to eachother are

homophilic, heterophilic binding and binding through an extracellular linker molecule

Tight junctions are made of

claudins

Adhesion belt are made of

cadherins

desmosomes are made of cadherins but differ from adhesion belt by

having bound intermediate filaments

Gap junctions are made of

connexins

Connexins will form

pores

The four basic cell-cell adhesions

tight junctions, adhesion belt, desmosomes, and gap junctions

cell-matrix adhesions

hemidesmosome and focal adhesions

Hemidesmosomes and focal adhesions are both made of

integrins

Adhesion belts differ from desmosomes by the presence of

actin filaments

Tight junctions are used for

occluding

Adherens junction and desmosomes are used for

anchoring

Gap junctions are used for

communicating

Hemidesmosome are used for

anchoring

Junctions can play a role in communication of

immune response and cancer cells or cancer to cancer cells

What is a nice example of various junctions and adhesions in tissue

in the lumen of the gut

Epithelium is the main barrier between

the GI lumen and the gut of the body

Connective tissue is made of

different types of junctions and are how the cell connect the tissues

Circular fibers are

perpendicular

Longitudinal fibers are

parallel

Connective tissue will maintain the

intestine as an organ and keep the fluid from leaking

Smooth muscle is arranged like

loops

In smooth muscle, one cell will contract and the other will

follow

Homophilic binding is with

same type of molecules on a neighboring cell

Heterophilic binding has a

angiogenic presentation with different molecules

Binding through an extracellular linker molecule is done by

molecule on a matrix that will use it as an anchor between two cells

Intermediate filaments will form

pores between two cells to allow small ionic molecules through

hemidesmosome will bind to

intermediate filaments

Focal adhesion will bind to

actin

Adhesion belt will anchor

junction (actin)

Desmosomes will bind to

different elements on the cytoskeleton

Tight junctions are found close to the

apical part of the cell

Tight junctions will selectively allow

glucose into our bodies

Tight junctions will enable

Na-K-ATPase-Driven secondary active transport of glucose

C-cadherin binding is through a

strand swapping mechanism

Without calcium, cadherins become

floppy and DONT bind

Cadherin with calcium will have

five repeating domains on the extracellular space

Cis-clustering of cadherins occurs when

cadherins will zip shut the membrane to be harder to break

Classical cadherins

Type I (e.g., E-cadherin) and Type II (e.g., N-cadherin)

Cadherin and Catenin can form

complexes

p120ctn tends to NOT bind to

cytoskeleton

B-catenin will

dimerize to bind to cytoskeleton

Tyrosine phosphorylation affects binding of proteins to

the cytoplasmic domain of VE-Cadherin

Phosphorylation patterns of VE-Cadherin affects pathway on the

intracellular side

Anchoring cell-matrix junction examples

focal adhesions and hemidesomosomes

Focal adhesions are made from

integrins

Focal adhesions will bind to different proteins, linking it to the

cytoplasm

Integrins can have

varying affinity (low, intermediate, and high)

The different conformational states of integrins defines their

binding

Two models of how integrins are activated

Switchblade model and deadbolt model

Different gap junctions display a variety of

size and charge selectivity

A function hyperemia leads to

increased blood flow and local Ca2+ release to near capillaries

Myoendothelial junction will undergo depolaization to be

transmitted to muscle cells

The cytoskeleton and junctions are thought to be a

sensor of physical forces

Tensegrity theory says

different types of structural elements are within the cell and malleable

Tensegrity structures are composed of parts that

are tensed working in opposition to other elements that resist being compressed

Tensegrity elements are balanced in such a way that

they tense and stabilize the entire structure

Tensegrity is the

architectural basis of cellular mechanotransduction

Integrated cell and cytoskeletal shape face a balance of

AMF, MT, and ECM

Severe muscular dystrophies and cardiac myopathies occur from

ECM, adhesion, or cytoskeletal mutations

Adhesions can act as a means for

cell trafficking and migration

Leukocytes can undergo

rolling, adhesion and extravasation

P-selectin is important for

leukocyte rolling