Diagram of Cell movement, extracellular matrix and junctions | Quizlet

What enables cell motility?

- Energy

- Extracellular components for mechanical interaction

- Guidance

'Crawling' cell motility is enabled by

Actin filaments

'Swimming' cell motility is enabled by

Microtubules

How many protofilaments in a microtubule?

13 protofilaments from a continuous hollow tube, heterodimer (alpha + beta)

What structures do microtubules form?

Network of unbranched and hollow cylinders...

Cilia and Flagella

Cilia enable...

The transport of extracellular fluids in the respiratory and reproductive tracts

Flagella enable...

The motility of sperm, protozoa and bacteria

Sizes of the cilia and flagella

Cilia are 2- 10 x 0.25 um

Flagella are much larger, at 100-200 x 0.25um

Axoneme

A vital structure found in eukaryotic cilia and flagella and responsible for their motion;

composed of two central microtubules surrounded by nine doublet microtubules

(9 + 2 arrangement)

Structure of the axoneme

9 + 2 pair

Radial spokes link outer doublets to inner pairs

Dynein arms

Outer doublets

share protofilaments

Dynein arms

resides in each pair of peripheral microtubules, makes the cilia move, using GTPto crawl up adjacent microtubules, bending cilia forward.

Nexin crosslinks

Structures which crosslink the dynein arms of the doublets, leading to flexion of the microtubule

What do nexin crosslinkers enable?

These structures crosslink the dynein arms of the doublets, leads to flexion of the microtubule

What does the inner arm of dynein enable?

Waveform characterisation of the power stroke

What does the outer arm of the dynein enable?

The power stroke

TERM

Basal bodies

DEFINITION

Structures which firmly root eukaryotic cilia and flagella at the cell surface

Basal body structure

Centriole structure is identical to basal bodies

They are composed of nine groups of fused triplet microtubules in a cartwheel

Actin based motility

In muscle based organisms, actin is involved in cellular motility

Difference between G and F actin

Globular and Filamentous

Describe the structure of the microtubule

Helical array of polymerized α- and β-tubulin (13 per circumference)

Polarised structure with a fast growing barbed + end, bound to GTP

Actin treadmilling

•A G-actin with an ATP bound associates at the PLUS end of an existing F-actin molecule

•ATP is then hydrolyzed to ADP

•A G-actin with an ADP bound tends to dissociate from the minus end of the polymer

Result: a shift in the position of the filament

Contrast actin and microtubules

Diameter of actin

5-9nm

Size of actin

42 kDa

Number of amino acids in actin

375

Diameter of microtubule

24nm

Size of tubulin

50kDa

Number of amino acids in microtubule

450

In which tubulin in GTP retained?

Alpha tubulin

Examples of actin binding proteins

→ Profilin inhibits nucleation

→ Accessory proteins regulate actin dynamics

→ Cofilin leads to filament fracture

Myosin

The contractile protein that makes up the thick filaments of muscle fibres

The motor in cytoskeletal or muscular contraction

What is the filament of a cilia or flagella? The Motor?

Microtubule filament, dynein motor

What is the filament of the cytoskeleton/muscle, and the motor?

Actin filament, myosin motor

Describe the structure of myosin

Each myosin molecule is shaped like 2 golf club twisted together. About 300 of them make up one thick filament. Myosin heads point away from the M line

Myosin power stroke

Action potential is transmitted across the neuromuscular junction (via the release of acetylcholine) and depolarises the sarcolemma. Waves of depolarisation spread down the T-tubules to trigger the release of Ca2+ ions from the sarcoplasmic reticulum

Ca2+ ions bind to troponin protein attached to tropomyosin and trigger a change in tertiary structure which reveals the actin-myosin binding site upon the actin myofilament

This allows the myosin head (with ADP and Pi attached) to form a myosin-actin crossbridge

An ADP molecule attached to the myosin head means that it is in the correct position to form the cross bridge

The myosin head changes angle and pulls the actin filament along, releasing ADP (and Pi)

This slides the actin myofilament along to shorten the sarcomere (the Z lines become closer together)

An ATP molecule binds to the myosin had, causing it to break crossbridge

Ca2+ ions activate ATPase which catalyses the hydrolysis of ATP to release ADP and Pi and energy required for the myosin head to return to its original position

The myosin head, once more with an attached ADP molecule reattaches further along the actin and the rachet mechanism repeats

Actin-based motility is enabled by...

Filopodium - finger like projection of actin

Lamellipodium- between the filopodium, crosslinked actin

Stress fibres- Contractile structures

Cortical actin- sheath around cell

Describe each of the structures which enable Actin-based motility

The filopodium is composed of parallel actin filaments

The lamellipodium is formed by crosslinked actin

Stress fibres are antiparallel contractile features

Cortical actin is a meshed sheath

Describe the directional motility of a cell

→ Growth factor or cytokine signals direction for filopodia projection

→ The lamellipodium is formed through signal activation

→ The cell presses forwards, extending, adhering to the factor

→ Contractile force is generated by actin stress fibres

→ Adhesions at back are disassembled and the entire cell contracts

What % of our bodies are cells?

~50%, the rest are various forms of extracellular matrix (ECM)

Features of ECMs

Extracellular matrixes are a meshwork of proteins and hydrated macromolecules

They regulate

...migration of cells, proliferation & specialisation and the shape of cells

ECM types

Fibrous

Adhesion

Hydrated macromolecules

Fibrous proteins

Collagen and Elastin

Adhesion proteins

fibronectin and laminin

Hydrated macromolecules

These are space filling sugars which hold water

Glycosaminoglycans (Gags)

Proteoglycans (Protein + Gag)

Collagen structure

Triple helices

Glycine-Proline-Hydroxyproline triplet repeats composed of 3 a chains

Where is collagen produced?

Fibroblasts and epithelial cells

How many varieties of collagen?

20-40

Collagen defects

Lead to Ehlers-danlos syndrome

Vascular form~

Arterial rupture

Collagen synthesis

A multistep, self assembly process dependent upon Vitamin C cofactors

Lots of Glycosylation and hydroxylation occurs

TERM

Elastin

DEFINITION

A protein that is similar to collagen and is the chief constituent of elastic fibres.

How does elastin assemble?

Self assembly through the conversion of tropoelastin to elastin by Lysyl oxidase

Relationship between elastin and fibrillin

Elastin is laid over a fibrillin scaffold

Elastin and Fibrillin are examples of...

Fibrous extracellular proteins

TERM

Glycosaminoglycans (GAGs)

DEFINITION

70-200 unit disaccharide chains which are highly charged and 'sticky'

TERM

Proteoglycan

DEFINITION

A glycoprotein containing a protein core with attached long, linear carbohydrate chains.

95% sugar, 80 saccharides

Glycoprotein

60% sugar

15 saccharides

TERM

Hyaluronan Complexes

DEFINITION

Hyaluronan is a large space filling molecule with aggrecan branches via. link proteins

Aggrecan is linked with chondroitin sulphate

Adhesion glycoproteins

protein-carbohydrate complexes that bind plasma membrane proteins to collagen and proteoglycans outside the cell wall.

TERM

Laminin

DEFINITION

is the protein found in the basement membrane to which integrins from cells attach

TERM

Fibronectin

DEFINITION

An extracellular glycoprotein secreted by animal cells that helps them attach to the extracellular matrix.

Coats a collagen scaffold to allow for cell adhesion and migration

Fibronectin structure

Two dimers linked by disulphide bridges

Cell binding, collagen binding and self-association domains

Cell binding domain has Arg-Gly-Asp RGD sequence

Cell binding site on Fibronectin

RGD sequence allows for polarity and adherence

Integrins

membrane proteins; they transmit signals between the ECM and cytoskeleton

How do integrins bind the ECM?

Divalent cations, removal causes cellular detachment

Focal adhesions

docking sites where cells adhere to their substratum and send signals to the cell interior

Focal adhesion components

→ Transmembrane receptor

→ Connection to cytoskeleton

→ Signalling

Knockout of focal adhesion proteins

B1 and A5 integrin knockouts are embryonic lethal

Fibronectin is day 9 lethal

Takin is 6-8 lethal

Integrin related defects

Platelet clotting, bleeding gums, LAD syndrome, impaired expression and recurrent bacterial infection

Ehlers-Danlos syndrome

Defective formation of collagen (risk for aortic dissection)

Marfan Syndrome

genetic connective tissue disorder that can cause a ruptured aorta

Related to fibrillin defects (the molecules which scaffold elastin)

LAD syndrome

Related to defects in B2 integrin

Leads to bleeding gums and vulnerability to recurrent bacterial infections

Cell Junction

structure that connects a cell to another cell or to extracellular matrix

Occluding junction

Type of cell junction that seals cells together in an epithelium, forming a barrier through which even small molecules cannot pass

Adherens Junctions

make an adhesion belt that keeps tissues from separating as they stretch and contract

Ca2+ dependent , homophillic interaction, strong intercellular links

Links to actin cytoskeleton

Adhesion belt

Found just below the tight junction, acts as a weak glue that holds cells together

Cadherin -> Catenin -> Actin -> Myosin

TERM

Desmosome

DEFINITION

a type of intercellular junction in animal cells that functions as a rivet, fastening cells together

Plentiful in heart muscle and epidermis

TERM

Hemidesmosome

DEFINITION

anchors intermediate filaments in a cell to the basal lamina

Via integrins and intermediate filaments

TERM

Integrin

DEFINITION

In animal cells, a transmembrane receptor protein with two subunits that interconnects the extracellular matrix and the cytoskeleton.

Cadherins

Calcium-dependent glycoproteins that hold similar cells together, extend the actin cytoskeleton to allow for adhesion between cells

Describe how cadherins in adherens junctions allow for the formation of tubular structures

A sheet of epithelial cells are linked by an adhesion belt (comprised of cadherins, catenin, actin and myosin)- these are E cadherins

N cadherins allow for invagination and pinching off to form a tubule

Pemphigus

autoimmune disease that causes skin blistering

Cadherins (desmoglein and desmocollin) which hold together keratinocytes are mutated

TERM

tight junctions

DEFINITION

prevent leakage of extracellular fluid across a layer of epithelial cells

Where are tight junctions found?

At the luminal junction between the cell and the lumen (apical face)

Function of tight junctions?

Prevent fluid, ion and membrane flow

Variable extent

(allow transport of some substances)

Transcellular transport

(transcytosis)

Paracellular transport

(diffusive)

What are tight junctions made of?

Occludin and Claudin

Defining membrane compartments

Specialised membrane regions are lipid and protein segregated

e.g.,

-Apical outer membrane

-Glycolipid

-Cholesterol

-Basolateral

-Phosphatidylcholine

Relates to membrane activity

TERM

Gap junctions

DEFINITION

provide cytoplasmic channels between adjacent animal cells, 100-500nm long and 2-4nm wide

Gap junction opening diameter

1.5nm

Gap of 2-4nm

Distribution of gap junctions

Connective tissue, epithelia, neurones and heart muscles

Gap junction structure

6 connexins make a connexon (each connexin has 4 TM parts)

Gap junction regulation

Membrane potential, pH, Ca2+ and cell signals

Gap junctions can be closed by dopamine, preventing the leakage of Ca2+ into adjacent neurones

Limit damage caused by calcium influx

Selectins

allow cells to adhere to carbohydrates on the surfaces of other cells and are most commonly used in the immune system