Beyond the cell: Cell Adhesions, cell junctions, and extracellular structures

Epithelium

sheets of cells that are polarized, with discrete functional domains at opposite ends of the cells

what are the two ends of cells?

apical and basal

Connective tissue

more loosely organized, in which cells are attached to each other, a rigid scaffold, or both

cell-cell junctions

specialized structures where two cells come together

Types of animal cell junctions

• adhesive junctions

• tight junctions

• gap junctions

plant cells have special structures called…

plasmodesmata

Adhesive junctions

anchor the cytoskeleton to the cell surfaces

what do adhesive junctions rely on?

specialized adhesion proteins

The extracellular portions of adhesion proteins on one cell can interact with…

the extracellular portions of similar proteins on the neighboring cells

Adherens junctions

desmosomes, these rely on intracellular attachment proteins to link the junction to the cytoskeleton

cadherins

on the outer surface bind cells to each other in adherens juctions

Adherens junctions

cadherin-mediated junctions that interact with actin; they are especially prominent in epithelial cells

what do adherens junctions rely on?

cadherins and their associated proteins to confer adhesion between cells

Cadherins are characterized by

• “repeats” in their extracellular domain that vary from protein to protein

• transmembrane domain

• widely varying cytosolic ends

E-cadherins

they have five repeats on its extracellular domain through with two E-cadherin moleculees can interact by (“zipping together”)

E-cadherins associate in pairs in teh plasma membrane, and their….

cytosolic portions interact B-catenin, a-catenin, then actin filaments

E-cadherins are found where

on epithelial cells

P-cedherins are found in where

in the placenta

Desmosomes

button-like points of strong adhesion between adjacent cells in a tissue

what do desmosomes provide tissues with?

structural integrity, they are abunant in skin, heart muscle, and the neck of the uterus

desmosome core

the extracellular space between the two connected cells

desmocollins and desmogleins

the desmosomal cadherins

Linker proteins such as B-catenins bind their cytosolic domains and…

link them to the cytoskeleton, e.g. intermediate filametns

Tight junctions

leave no space between the plasma membranes of adjacent cells

Why do epithelial cells need tight junctions?

they need specialized structures to seal them tightly together

How are tight junctions formed?

they form a continuous belit around the apical ends of lateral surfaces of each cell; molecules cross the cell layer by passing through the cells

Tight junctions contain several major…

transmembrane proteins such as occludin and immunoglobulin superfamily proteins called junctional adhesion molecules

Tight juctions also contain claudins, which are

four membrane-spanning domains

Claudins i adjacent cells are thought to interlock to form a tight seal, how?

the large extracellular loop forms ion-selective pores to allow passage of specific ions

paracellular transport

most likely regulated by claudins, the ions move between cells, made of ion selective pores

tight junctions also block lateral movement of…

lipids and proteins in the plasma membrane

what is movement of lipids blocked by?

the outer monolayer

movement o integral membrane proteins is…

completely blocked

gap junction

a region where the plasma membranes of cells are aligned and brought into the contact, with a very small gap between

the gap in a gap junction is spanned by….

small pipelines or passages between the cells

small molecules and ions can pass directly from…

one cell to another in tight junctions

at a gap junction, the plasma membranes of adjacent cells are joined by…

hollow cylinders called connexons

each connexon is an assembly of what?

six subunits of connexin proteins that form a circle

each connexon has a channel of about…

3nm wide, too small to allow proteins, nucleic acids, or organelles to pass through

different tissues have different types of connexins…

but they all function the same way

Bone

consists of mainly rigid extracellular matrix that contains. small number of interspersed cells

cartilage

a tissue constructed mostly of matrix materials that is more flexible than bones

connective tissue

surrounding glands and blood vessels is relatively gelatinous and contains interspersed fibroblast cells

Three classes of ECM molecules

• structrual proteins

• protein-polysaccharide complexes

• adhesive glycoproteins

structural proteins

provide strength and flexability

ex) collagens and elastins

protein-polysaccharide complexes

provide the hydrated matrix

ex) proteoglycans

Adhesive glycoproteins

allow cells to attach to the matrix

ex) fibronectins and laminins

Collagen

• secreted by several types of cells in connective tissue including fibroblasts

• most abundant ECM component in animals

Collagen fibers

the fibers of collegan, are enormously strong and are composed of numerous fibrils

Each fibril is made of many collagen molecules, each

is composed of three a chains twisted into a helix

Procollagen

a triple helix that three chains asseble to form in the lumen of the ER, they have short nonhelical sequences at both ends

Once procollagen is secreted out of the cell it is cleaved by…

procollagen peptidase to remove both ends of the molecule

resulting collagen molecules spontaneously associate into

fibrils and then fibers

the stability of collagen fibrils is reinforced by

hydrogen bonds within and between collagen molecules

elastins

provide elasticity to the ECM by being a stretchable elastic fiber

Elastins are rich in…

glycine and proline, the molecules are crosslinked by bonds between lysine residues

Tensio causes the overall elastin network to stretch, the release of tension…

causes individual molecules to relax

collagen and elastin fibers are enmeshed in a gel like networ of…

proteoglycans, which are glycoproteins with a lot of glycosaminoglycans

Glycosaminoglycans (GAGs)

large carbohydrates with repeating disaccharide units

Most common types of glycosaminogylcans

chondroitin sulfate, keratan sulfate, and hyaluronate

what forms proteoglycans

glycosaminoglycans in the ECM get covalently bound to proteins

each proteoglycan has a number of GAG chains attached along…

the length of a core protein

proteoglycans vary greatly in size dependig on the size of the…

core protein and the length of the carbohydrate chains

proteoglycans are usually integral components of the…

plasma membrane, with their core polypeptides embedded in the membrane

in many tissues, proteoglycans are…

present as individual molecules

in cartilage, numerous proteoglycans become…

attached to long molecules of hyaluronate

direct links between the ECM and the plasma membrane are reinforced by

a family of adhesive glycoproteins that have multiple domains to bind molecules in the ECM and receptors on membranes

laminins and fibronectins are

the most common types of adhesive glycoproteins

fibronectins

family of cloesly related glycoproteins in the ECM

what does a fibronectin molecule consist of?

two large subunits linked near the C-terminals by two disulfide bonds

each fibronectin subunit is folded into what?

a series of rodlike domains

several domains bind one or more ECM macromolecules including..

several types of collagen, heparin, and fibrin

fibronectin acts as what?

a bridging molecule between cells and the ECM

laminins are found mainly in

the basal lamina

basal lamina

a thin sheet of specialized extracellular material

the basal lamina underlies epithelial cells, separating them from

connective tissues

What is the basal lamina?

a structural support and a permeaility barrier

All forms of basal lamina contain type IV…

collagen, proteoglycans, laminins, and another glycoprotein called entactin or nidogen

cells can alter the properies of the basal lamina by…

secreting enzymes that catalyze changes in the lamina, such as matrix metalloproteases (MMPs)

Integrins

large family of cell surface recdeptos that bind to fibronectins or laminins

Integrins integrate the…

cytoskeleton with the ECM

An integrin consists of what?

two large transmembrane polypeptides, alpha and beta

there are multiple types of alpha and beta subunits, resulting in

types of integrin heterodimers

Many integrins recognize the RGD sequnces…

in the ECM glycoproteins they bind

integrin tails interact with cytosolic proteins that do what?

link integrins to cytoskeleton

migratory and non-epithelial cells (fibroblasts) attach to…

ECM molecules via focal adhesions

focal adhesion contain clustered integrins that interact with…

bundles of actin filaments via talin, vinculin, and alpha actinin

Hemidesmosomes, where are they found?

in epithelial cells; they contain a6B4 integrin, where integrins are attached to keratin

plakins

the linker proteins in hemidesmosomes that form a dense plaque connecting the integrins to the cytoskeleton

costamere

an attachment structure at the surface of striated muscle

costameres contain many of the same proteins found at….

focal contacts in addition to the protein dystrophin

plasmodesmata

cytoplasmic channels through openings in the cell wall, allowing cytoplasmic continuity between two adjacent cells

plasmodesma is lined with plasma membrane common to the…

two cells, with the desmotubule in the central channel

the annulus lies between the…

desmotubule and membrane lining the plasmmodesma

what do plasmodesma function like?

they function like gap junctions