Cell adhesion 4 new

what are selectins?

carbohydrate binding cell adhesion molecules involved with leukocytes

what type of binding is there with selectins?

heterophillic - selectins bind specific sugars on glycoproteins

what are the 3 types of selectins?

L-selectin, E-selectin , P-selectin

where is E-selectin expressed?

on activated ednothelial cells in response to inflammation 

what is the role of L-selectin?

important for lymphocytes

what type of binding occurs during the leukocyte rolling?

weak, transient binding between selectins and carbohydrate ligans which causes rolling along the endothelium

what are integrins?

transmembrane adhesion receptors that bind ECM or cell-surface ligands and link them to the cytoskeleton

what type of binding do integrins use?

heterophillic binding (e.g. integrin binding to fibronectin)

what are the 2 main subunits of integrins?

alpha and beta subunits

in which state are integrins normally in?

low affinity inactive states

how are integrins activated?

through inside-out signalling or outside -in signalling

what ECM components do integrins bind?

collagen, laminin, fibronectin

what are focal adhesions?

large integrin rich structures linking the ECM to actin

what is integrin clustering?

the gathering of multiple integrins in one area to increase the adhesive strength

what does outside-in signalling regulate?

cell survival, proliferation, migration and cytoskeletal organisation

what is the leukocyte adhesion cascade?

multi step process allowing leukocytes to exit the bloodstream and enter tissues during inflammation

what are the steps of the leukocyte adhesion cascade?

1. rolling

2. activation

3. firm adhesion

4. diapedesis

   1. migration

which molecules mediate leukkocyte rolling?

selectins - E,P,L

what is diapedesis?

leukocytes squeexing between endothelial cells to enter tissues

what condition results from defective leukocyte adhesion?

leukocyte adhesion deficiency (LAD) which leads to recurrent bacterial infections

what is inside out signalling with integrins?

intracellular signals which change the integrin to a high affinity conformation

what is outside in signalling with integrins?

when ligand binding triggers changes in the cytoskeleton and cell behaviour

what is an activator of inside out signalling with integrins?

talin

how does integrin activation affect the cytoskeleton?

it induces actin rearrangements, cell spreading or strengthening of adhesions

how do integrins influence cadherin adhesions?

strong integrin adhesion can promote adherens junction formation by stabilising actin networks

how do cadherins influence integrin signalling?

E-cadherin can reduce integrin activation and limit cell migration

why is it important that there is integrin cadherin interactions?

it regulates epithelial stability and migration (e.g. wound healing or metastasis)

what is the main adhesive glycoprotein linking cells to the ECM?

fibronectin

what is the role of focal adhesions?

anchor cells to the ECM

what happens when integrins fail to activate properly?

theres impaired immune cell adhesion →infections→LAD

how does cancer use integrins?

tumours alter integrin expression to enance migration and survival