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21 Cards in this Set

  • Front
  • Back
what is the structure of a Laminin
Laminins are glycoproteins Three similar polypeptide chains linked by disulfide bridges organised into a cross shape.
what can laminins do
Like fibronectin, laminins can cross link the proteins in the ECM

Laminins can also bind tightly to receptor proteins on the surface of cells and play a role in guiding cells through the ECM and in binding cells to substrata during the migration of cells that occurs during embryonic development.
what are Integrins
receptor proteins on cells that bind to ECM
I-domain
The extracellular ends of the integrin subunits terminate in “I-domains” –domains which bind to “ligands” in the extracellular space (other proteins or signalling molecules)
what do The intracellular ends of integrin subunits do
The intracellular ends bind adaptor proteins, such as vinculin, that connect them to the actin-based membrane skeleton.

Thus the cytoskeleton becomes mechanically linked through the integrins to the ECM substratum
Functions of integrins
1) Mechanical linkage of cytoskeleton to the substratum

2) Signaling the presence of ligands (e.g. cell guidance proteins during developmental migration).
how does an intergrin signal the presence of a ligand
the conformational change in integrin upon binding a ligand is passed on via the cytoskeleton to a chain of protein kinases.

The protein kinases phosphorylate other proteins which:

Activate cellular events directly

Alter the rate of transcription of genes and therefore alter the expression of proteins that control the behavior of the cell (motility, secretion, growth, division)
how does an integrin bind an extracellular ligand
Most extracellular proteins that bind to integrins have an RGD motif

About half of all integrins contain a RGD binding-site and so can bind to any of these ligand proteins.
what can Artifical peptides containing the RGD sequence do
they can be used to interfere with the ability of integrins to bind ligands.

These peptides will, therefore, interfere with the the ability of cells to interact with the extracellular matrix or the ability of cells to aggregate with each other.

Drugs based on these peptides may be useful to prevent, for example, blood clotting.
what is a hemidesmosome
A structure in which intermediate filaments are connected via a dense protein placque to integrins and thence to anchoring laminins and collagen fibers in the substratum (see Fig. 7.18)
what do Hemidesmosomes do
Hemidesmosomes attach epidermal cells in the skin to the underlying basement membrane
How is the recognition of one cell type achieved by another?
Presumably it requires an array of ligand molecules on the surface of each cell type that defines what type of cell it is.

These recognition ligands may be either proteins or arrangements of sugars in the cell coat of target cells.

….. and an array of receptor proteins on the surface other cells that bind to those ligands and initiate adhesion.
what are the Proteins which mediate cell-cell adhesion
Selectins

Immunoglobulins

Integrins

Cadherins
what are Selectins
A family of integral membrane glycoproteins with extracellular domains that recognize and bind to particular arrangements of sugars in the polysaccharides comprising the cell coat (glycolcalyx) of other cells.
what does the Binding of selectins to sugars require
the presence of calcium ions in the extracellular space
what do Immunoglobulins mediate
the interactions of lymphocytes with other cells required for the immune response.

Adhesions between certain types of nerve cells (NCAM, L1)

Adhesions between certain other special cell types
what can mutations in the IgSF cause?
Mutations in the human IgSF, L1, which mediates adhesions of certain nerve cells can result in hydrocephaly, mental retardation and spasticity due to the failure of some nerve tracts in the brain to grow properly.
what are Cadherins
A large transmembrane glycoprotein family that mediate adhesion of similar cells together –similar cadherins bind to each other.
adherens junctions
Arrays of cadherin molecules and the underlying membrane skeleton form “adherens junctions” that bind together , for example, cells lining blood vessels.
catenins
linker proteins which tether the intracellular domains of cadherins together, so the binding of one cadherin to another can trigger events inside the cells.
in relation to cadherins what does an aggregation of cells do
aggregation of cells can trigger changes in the functions of cells that are appropriate to their new role in a tissue with other cells. Communication between cells in the tissue is also possible via their adherens junctions –allowing the tissue to respond “en masse” to a stimulus received by only a few cells