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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 |
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What do intermediate filaments do? |
link one cell to another -like ropes -hold cells together -many are cell type specific |
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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 |
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What are keratins? |
intermediate filament holds epithelial cells together in skin |
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What do desmins do? |
links muscle cells together intermediate filaments |
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What does vimentin do? |
in mesenchymal cell (migratory cell) e.g. fibroblast -helps hold things together as the cell migrates |
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What do the neurofilaments do? |
found in neurons, axons, dendrites holds things together |
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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 |
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What is lamin? |
found in the nucleus of all cells holds up the nuclear envelope gives spaces for the nucelus to have stuff |
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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 |
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How do we know that intermediate filaments are dynamic? |
proteins (biotin keratin subunit) within filament are exchanged -cytoskeleton is always changing |
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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 |
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How are the dynamics of IFs regulated? |
balancing of actin of kinases (CDKs) and phosphotases crucial |
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Match - microtubules are made of? |
tubulin |
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Match- Microfilaments are made of ? |
actin |
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What are some IF associated proteins? |
plectin (green) cross-links IF vimentin (blue) and microtubules (red) |
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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 |
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What is plectin? |
an intermediate filament associated protein cross links vimentin and microtubules (also a microtubule associated protein) |
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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) |
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What does LAP2 (intermediate filament associated protein) do? |
it links lamin A & B to nuclear lamina (nuclear envolope) |
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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 |
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What can ankryin bind to? |
actin cytoskeleton & IF cytoskeleton to plasma membrane |
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What happens in keratin mutations? |
transgenic mice carrying a mutant keratin gene exhibit skin blistering - weak skin integrity dermis can separate from epidermis!! :( |
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What do epithelial cells form? |
the dermis |
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What are desmosomes and hemidesmosomes? |
IF junctions IFs are anchored to them |
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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 |
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What are desmosomes? |
IF junction protein cell-cell junctions (link keratin in epithelial cells) involves cadherins! |
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What are hemidespomes ? |
IF junction protein cell-ECM junctions |
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Which IF junction is cell-ECM? |
hemidesmosomes (basal surface) |
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Which IF junction is cell-cell junction? |
desmosomes |
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how does keratin work with desmosomes? |
goes through them through the epithelial cells |
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What is the outside surface of epithelial cells called? |
apical surface (top) opposite of ECM (basal bound to ECM) THEREFORE HAVE polarity |
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What is the job of epithelial cells? |
be a barrier -prevent things from entering transferring schizt from apical surface to basal surface |
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What are the 4 types of adhesions that epithelial cells use? |
gap junctions tight junctions cell-cell cell-ecm |
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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 |
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What can the cytoplasmic domain of E-cadherin bind to? |
cytosolic with cytoskeleton the extracellular domain to cadherin on the other cell |
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What does the hemophilic interaction between cadherins in the ECM require? |
Ca2+ dependent binding almost unlimited in ECM tho! no problem |
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What is the point of Ca2+ dependent binding between cadherins in the ECM? |
essential for hilding cells in sheets E-cadherin for epithelial |
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Where can we find E-cadherin? |
non-neural epithelial tissue preimplantation embryos |
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Where can we find P-cadherin? |
trophoblast |
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Where can we find N-cadherin? |
Nervious system, lens,cardiac and skeletal muscle |
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How do Cadherens do cell adhesion? |
cadherins + IFs(keratin) = desmosomes |
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What do cadherens form when they bind to actin cytoskeleton? |
adherens junction |
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What do adherens junctions tell u? |
that there is cadheren bound to actin cytoskeleton |
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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 |
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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 |
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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 |
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What is N-CAM? (neuro) |
IG superfamily homophilic mediate Ca2+ indepedent homophilic cell adhesion GPI anchor |
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Big difference between N-CAM and Cadherins? |
Cadherins - Ca2+ dependent binding N-CAMs - Ca2+ independent biding |
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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 |
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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 |
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What are the two molecules involved in heterophilic interaction? |
Selectins & Integrins |
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What do selectins do? |
-recognize oligosaccharides, bind to sugar -participate in leukocyte extravasation (P-selectin) |
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What are leukocytes? |
-white blood cells -will have a specific sugar on them -recognized by P-selectin (recognize the sugar) |
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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 |
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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 |
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How are endothelial cells held together? |
by iCAM molecules, homophilic interactions |
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How do iCAM molecules and integrins work? |
the integrins recognize the iCAM molecules |
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How is the leukocyte bound to the endothelial cell? |
two ways: 1. via P-selectin 2. via integrins & iCAM |
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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 |
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What is integrin...? |
binds to ICAM heterophilic molecule made of a heterodimer = alpha & betasubunits |
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What does alpha1 & beta1 bind? (integrins) |
collagen |
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What does alpha5 & beta1 bind (integrins) bind? |
fibronectin |
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What does alpha6 & beta1 bind (integrin) bind? |
laminin |
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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 |
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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 |
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Do ICAM molecules have RGD sequence in them? |
YES otherwise integrins wouldnt bind to them.. specific alpha beta |
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How can integrins be? |
in an active or inactive form -they are in different shapes |
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Beside being on leukocyotes and binding ICAM what else can integrins do? |
can transduce cell signals |
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what regulates whether an integrin can bind or not? |
the cell, can activate or inactivate it |
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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 |
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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 |
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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 |
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Why do focal adhesions require integrins? |
integrins that bind to the actin cytoskeleton are called focal adhesions |
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integrins that bind to intermediate filaments are called? |
hemidesmosomes |