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75 Cards in this Set

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How are intermediate filaments different?

not globular


large proteins


no ATP or GTP needed


no polarity


no known motor proteins


less dynamic


great tensile strength


cell and tissue integrity

What do intermediate filaments do?

link one cell to another


-like ropes


-hold cells together


-many are cell type specific

What are the four types of intermediate filaments that we need to memorize?

1. keratin - epithelial cells




2. desmin - muscle cells




3. vimentin - mesenchymal cells




4. neurofilaments -neurons




5. lamins (not cell specific) - nuceus

What are keratins?

intermediate filament


holds epithelial cells together in skin



What do desmins do?

links muscle cells together


intermediate filaments



What does vimentin do?

in mesenchymal cell (migratory cell)


e.g. fibroblast




-helps hold things together as the cell migrates

What do the neurofilaments do?

found in neurons, axons, dendrites holds things together

How can intermediate filaments help with cancer?

looking at what kind of intermediate filaments a cell has can help us identify what kind it is even though it is cancerous

What is lamin?

found in the nucleus of all cells


holds up the nuclear envelope


gives spaces for the nucelus to have stuff

What is the structure of intermediate filaments?

1. basic unit is a tetramer


2. tetramer is NOT POLAR but is symmetrical


3. has N-terminus & C-terminus


4. tetramer: Head, ROD, TAIL (two dimers)


5. tetramer polymerize and get protofilament



How do we know that intermediate filaments are dynamic?

proteins (biotin keratin subunit) within filament are exchanged




-cytoskeleton is always changing



Why are IFs dynamic?

-need to disassemble during mitosis (CDKs )


***phosphorylation of MAPS during mitosis by CDKs gets rid of microtubules




-N-terminal domain of lamin A phosphorylated (by CDKs) at serine-induces disassembly, and prevents reassembly. -> nuclear envelope breaks




-mutation of this serine causes nuclear envolope not to break b/c lamine remains intact - no dissamsembly

How are the dynamics of IFs regulated?

balancing of actin of kinases (CDKs) and phosphotases crucial

Match - microtubules are made of?

tubulin

Match- Microfilaments are made of ?

actin

What are some IF associated proteins?

plectin (green) cross-links IF vimentin (blue) and microtubules (red)





What is the role of IF associated proteins?

ONLY ORGANIZATIONAL link IFs to many other thing- most that we know in structural stuff ( to membranes or other proteins)


e.g. cross-linking




NO motor




NO cap




NO severing

What is plectin?

an intermediate filament associated protein




cross links vimentin and microtubules (also a microtubule associated protein)

What types of functions do IFs have? specifically lamins?

lamins support nuclear membrane




LAP2 (lamin associated polypeptide) - an intermediate filament associated protein links Lamins A&B (form network) to nuclear envolope (lamina)

What does LAP2 (intermediate filament associated protein) do?

it links lamin A & B to nuclear lamina (nuclear envolope)

What are types of functions do lamins have?

provide structural support necessary for cell shape (cell membrane/plasma membrane)


e.g vimentin links to ankryin




vimentin binds to ankryin and to the plasma membrane



What can ankryin bind to?

actin cytoskeleton & IF cytoskeleton


to plasma membrane

What happens in keratin mutations?

transgenic mice carrying a mutant keratin gene exhibit skin blistering - weak skin integrity




dermis can separate from epidermis!! :(

What do epithelial cells form?

the dermis

What are desmosomes and hemidesmosomes?

IF junctions




IFs are anchored to them

What keeps the epithelial cells tightly bound together to from a barrier?

lipid bilayer is not strong




keratin that is found in epithelial cells go from cell to cell through desmosomes (between cells) - protein junctions



What are desmosomes?

IF junction


protein


cell-cell junctions (link keratin in epithelial cells)




involves cadherins!

What are hemidespomes ?

IF junction


protein


cell-ECM junctions

Which IF junction is cell-ECM?

hemidesmosomes




(basal surface)

Which IF junction is cell-cell junction?

desmosomes





how does keratin work with desmosomes?

goes through them through the epithelial cells

What is the outside surface of epithelial cells called?

apical surface (top)




opposite of ECM (basal bound to ECM)




THEREFORE HAVE polarity

What is the job of epithelial cells?

be a barrier -prevent things from entering




transferring schizt from apical surface to basal surface

What are the 4 types of adhesions that epithelial cells use?

gap junctions


tight junctions




cell-cell




cell-ecm

What does it mean if a cell has E-Cadherin?

they are homodimers


they are transmembrane proteins


40 types of cadherins


E-cadherins can only bind to E-cadherin

What can the cytoplasmic domain of E-cadherin bind to?

cytosolic with cytoskeleton




the extracellular domain to cadherin on the other cell

What does the hemophilic interaction between cadherins in the ECM require?

Ca2+ dependent binding




almost unlimited in ECM tho! no problem

What is the point of Ca2+ dependent binding between cadherins in the ECM?

essential for hilding cells in sheets E-cadherin for epithelial

Where can we find E-cadherin?

non-neural epithelial tissue


preimplantation embryos

Where can we find P-cadherin?

trophoblast

Where can we find N-cadherin?

Nervious system, lens,cardiac and skeletal muscle





How do Cadherens do cell adhesion?

cadherins + IFs(keratin) = desmosomes

What do cadherens form when they bind to actin cytoskeleton?

adherens junction





What do adherens junctions tell u?

that there is cadheren bound to actin cytoskeleton

What do adherens junctions form when they come together?

circumferential belt = contract that cell, change shape of belt and change shape of top of cell and tissue

Why does the cell want both an intermediate filament cytoskeleton and an actin one?

the IF one keratin - is tensile provides strength




actin one - has motors... can move things around! form belt

Why are there adaptor proteins between cadherens and cytoskeleton?

it tells nucleus that it is bound to another cell, adaptor protein can tell the nucleus that they are no longer in contact if something bad happens

What is N-CAM?


(neuro)

IG superfamily




homophilic




mediate Ca2+ indepedent homophilic cell adhesion




GPI anchor

Big difference between N-CAM and Cadherins?

Cadherins - Ca2+ dependent binding




N-CAMs - Ca2+ independent biding

What is special about N-CAMs?

IG-superfamily is very variable




some of them do not have transmembrane domain (no cytoplasmic domain)




linked to plasma membrane (cell) by GPI anchor

What does it mean for N-CAM IG superfamily protein doesnt have cytoplasmic domain?

has GPI anchor




BUT! it cannot signal to he nucleus if you break cell-cell adhesion

What are the two molecules involved in heterophilic interaction?

Selectins & Integrins

What do selectins do?

-recognize oligosaccharides, bind to sugar


-participate in leukocyte extravasation (P-selectin)



What are leukocytes?

-white blood cells


-will have a specific sugar on them


-recognized by P-selectin (recognize the sugar)





Steps of extravasation?

1. Endothelial cells in blood vessels recognize signal from infection site -> secrete P-selection on cell suface




2. P-selection binds to to carbohydrates on leukocytes & slows down leukocyte




3. Need more adhesion to get the leukocytes through the endothelial cell -> integrins on leukocyte



What do the integrins on the leukocyotes do?

they are on the leukocyte


recognize molecules on the endothelial cells


iCAM molecules on the leukocyte - Ig superfamily





How are endothelial cells held together?

by iCAM molecules, homophilic interactions



How do iCAM molecules and integrins work?

the integrins recognize the iCAM molecules



How is the leukocyte bound to the endothelial cell?

two ways:




1. via P-selectin


2. via integrins & iCAM

What allows extravasation to happen?

ultimately it's the firm adhesion of the leukocyte to endothelial cell via integrin/iCAM binding in addion to the P-selectin one

What is integrin...?

binds to ICAM


heterophilic molecule


made of a heterodimer = alpha & betasubunits

What does alpha1 & beta1 bind? (integrins)

collagen

What does alpha5 & beta1 bind (integrins) bind?

fibronectin

What does alpha6 & beta1 bind (integrin) bind?

laminin

What does the core of the integrin molecule alpha & beta recognize?

all of the recognize a core amino acids that is RGD ( arginine glycine aspartic acid)




INTEGRINS WILL BIND TO A PROTEIN IF IT HAS A RBD Polypeptide

If all integrins recognize the core RGD what gives them specificity in binding?

the proteins around RGD - different integrins will only bind to different molecules

Do ICAM molecules have RGD sequence in them?

YES otherwise integrins wouldnt bind to them..


specific alpha beta





How can integrins be?

in an active or inactive form




-they are in different shapes

Beside being on leukocyotes and binding ICAM what else can integrins do?

can transduce cell signals

what regulates whether an integrin can bind or not?

the cell, can activate or inactivate it

In a leukocyte how is an integrin activated?

the leukocyte activates it after P-selectin is secreted by the endothelial cell and it binds to the sugar on the leukocyte




thennn the cell activates integrin binds to ICAM

How is integrin liked to the cytoskeleton?

integrin is a transmembrane protein, it's cytoplasmic tail is liked to the actin cytoskeleton




->>>>>> leading edge of the cell has integrins on it!!!!




->>> cause signalling cascade

We know that filapodia and lampelopodia look for places to bind when looking for focal adhesions.... what are they looking with?

with integrins! that leading part of the cell has integrins in it




if the cell wants to bind to laminin it uses a alpha6beta1



Why do focal adhesions require integrins?

integrins that bind to the actin cytoskeleton are called focal adhesions





integrins that bind to intermediate filaments are called?

hemidesmosomes