LM 7.5: Cell Motility Flashcards

Question

what are the specific steps in extravasation and which molecules are involved in each?

Answer 1

1. leukocytes just floating through the blood stream 2. endothelial cells receive a signal to being to activate - can come from chemokines from immune cells or from an injured cell 3. platelet activation factor and P-selectin are expressed on the endothelial surface 4. P-selectin grabs onto leukocytes by binding to S-lewis X, but this is a transient bond so this is why the leukocytes just roll along the blood vessel wall 5. leukocytes are activated and the PAF receptor on the leukocyte binds to PAF on the endothelial cell 6. integrin on leukocyte is fully activated and binds to ICAM (intracellular adhesion molecule) which arrests the leukocyte on the endothelial cell and polarizes it 7. leukocyte undergoes trans endothelial migration led by integrins and the secretion of enzymes that act like scissors to cut a path along the underlying tissue for cells to migrate upon - the leukocyte has lamellapodia or pseudopodia that push between adjacent cells

Answer 2

transmembrane proteins that bind ECM ligand and link the outside ECM to the cell's actin cytoskeleton

Answer 3

they are transmembrane proteins that are heterodimers made of one α and one β subunit there's an extracellular ligand binding domain and a cytoplasmic tail on the inside of the cell that will hook into the actin cytoskeleton there's tons of different α and β subunits and they all mix and match with each other - the specific dimer formed dictates which extracellular ligand it can bind

Answer 4

there's tons of different α and β subunits and they all mix and match with each other - the specific dimer formed dictates which extracellular ligand it can bind possible ECM ligands: collagen, fibronectin, laminins, VCAMs

Answer 5

integrins usually have relatively low binding affinities for their ligand it takes weak binding of numerous integrin molecules to give the cell a firm hold onto the ECM = clustering!! this is actually helpful when it comes to cell migration because if the bonds were too strong the cell wouldn't be able to move

Answer 6

signals are generated from either the inside of the cell or the outside of the cell these signals tell the integrin to activate and change conformation so that it can bind its ligand

Answer 7

linking the ECM to the intracellular cytoskeleton

Answer 8

once integrins cluster, the assemble a network of proteins on the inside of the cell, linking the integrin cytoplasmic tail with the actin cytoskeleton = focal complex so forces exerted on the outside of the cells through compression of tissue can be transduced to the inside of the cell through the integrin-actin linkage which will cause the cell to alter cell signaling or gene expression to respond to its environment

Answer 9

we need to make sure integrin mediated adhesion is working because it's what allows the cell to adhere and move! if this system is messed up, it's usually due to mutations or defects in genes encoding integrins

Answer 10

alpha II betaIII heterodimer is mutated/absent which leads to a defect in fibrinogen binding and lack of clotting integrin on platelets is unable to bind to fibrinogen to participate in clotting! this is a disease effecting integrin! this is a disease that effects integrin!

Answer 11

LAD = leukocyte adhesion deficiency a variety of integrins including B1,2 and 3 are missing or mutated this disallows cells from interacting with ECM proteins so these cells can't be recruited to sites of injury or infection

Answer 12

migration between endothelial cells of the blood vessel into the tissue

Answer 13

migration through a pore in an individual endothelial cell of the blood vessel into the tissue

Answer 14

intravasation = cell entering the blood stream through the endothelium extravasation = cell leaving the blood stream through the endothelium diapedesis = cell traveling through the endothelium to leave the blood stream into the tissue

Answer 15

diapedesis usually requires molecular scissors called MMP to gain access to underlying tissues the basement membrane is made up of ECM proteins that are tightly woven and hard to get though! cells are much bigger than the holes in the basement membrane so they need to cut their way through with MMPs MMPs are secreted enzymes that the tumor cells or immune cells spit out MMPs digest basement membrane and ECM so that cells can gain access to underlying tissues

Answer 16

contraction and tension!! it's a traction driven model!! 1. leading edge extends in the form of an actin-enriched protrusion called a lamellipodia/filopodia 2. F-actin polymerization creates force to push upon the plasma membrane to deform it into an extension 3. the cell makes an integrin-dependent adhesive contact with the underlying substrate, via formation of focal contacts 4. rear end of the cell must disengage in order to allow for forward motion so focal contacts are severed and there's a myosin II-based contraction even to snap the rear forward 5. further extension of the lamellapodia until the cell gets to where it wants to go

Answer 17

bits of migrating cells that are left behind on the substrate that can act as breadcrumbs to guide other migrating cells