Quiz 2 review lecture flashcards
What junction prevents extraceullular molecules from leaking from one side of an epithelium to the other
Tight junctions
What junctions allows cells to interact with their neighbours
Gap junction
Hemichannel
When a connexon from one cell does not line up with one from another cell, opens up to extracellular space - essentially a pore that can allow ions in and out of cells
The extracellular space is occupied by an intricate network of macromolecules constituting the
Extracellular matrix
The matrix is composed of various ______ and ____________
Proteins and polysaccharides
In our bodies, the most plentiful forms of extracellular matrix are found in
Bulky connective tissues such as bone, tendon and the dermal layer of the skin
True or false: The basal lamina is the underpinning of all epithelia
True
2 Tissues of basal lamina is found
muscle and epithelium
Muscle tissue basal lamina
Basal lamina wraps around cells and follows muscle path
Epithelium basal lamina
more polar in organization – there is a sheath of villi on the top and the basal surface is attached to the basal lamina which is right above connective tissue
Basal lamina cell functions
-determines cell polarity
-influences cell metabolism (controls directional flow of nutrients)
-organizes the proteins in adjacent PM
-promote cell suvival, proliferation, differentiation
Mechanical role of basal lamina (skin)
The epithelial outer layer (epidermis) depends on the strength of the basal lamina to keep it attached to the underlying connective tissue (dermis)
2 essential components of the basal lamina
Laminins and type IV collagen
Laminins role basal lamina
Primary organizer of the sheet structure, the basal lamina consist primarily of laminin molecules
Type IV collagen role basal lamina
Gives basal lamina tensile strength.
How does the basal lamina act like a filter
The kidney glomerulus has an unusually thick basal lamina that acts as a molecular filter preventing the passage of macromolecules from the blood into the urine.
Matrix in connective tissue and basal lamina: Two main classes of macromolecules they are cosntructed from
1) glycosaminoglycan (GAG) polysaccharide chains usually covalently linked to proteins in the form of proteoglycans
2) fibrous proteins such as collagen
Polysaccharide role ECM
Resist compressive forces on the matrix while permitting rapid diffusion of nutrients, metabolites and hormones between the blood and tissue cells
Collagen fibers role ECM
Strengthen and organize matrix, while other fibrous proteins such as elastin (rubber-like) give it resilience
The ability to cut through the matrix is crucial in two ways:
1) it enables cells to divide while embedded in the matrix
2) it enables them to travel through it
Why is the ability to cut through matrix required by white blood cells
To cross the basal lamina of blood vessels into tissues in response to an injury
Cells degrade matrix components through extracellular ________
proteases
Two general classes many proteases belong to:
1) matrix metalloproteases, which depend on bound Ca2+ and Zn2+
2) serine protease, which have a highly reactive serine in their active site
Three basic control mechanisms of proteases
Local activation: Activate inactive proteases, plasminogens become active when cleaved by plasminogen activators, active plasmin helps break up blood clots
Confinement by cell-surface receptors: Cell-surface receptors bind to proteases confining the enzyme to where it is needed
Secretion of inhibitors: Secretes protease inhibitors
Fibronectin role
Helps cells attach to matrix
Mutant mice that cant secrete fibronectin: what happens?
Die early because their endothelial cells are unable to form proper blood vessels
RGD binds to cells through an
RGD motif that binds integrins
Outside-in signalling
Signal comes from outside and transduced into the cells
- the stimulus binds to that RGD domain in fibronectin, causes a structural change which now the talin binding domain becomes revealed
-This allows for the integrin that is bound to fibronectin in the EMC to be linked to the cytoskeleton of the cell
-Talin is the connection that links integrin to the cytoskeleton
Inside-out activation
Example: Ligand binds to RTK – dimerization – transautophosphorylation, formation of docking sites to initiate the signalling cascade
-PIP2 is phosphorylated to pip3
(It is possible that PIP2 OR PIP3 can change the structure of talin) so that it opens talin binding sites to bind to integrin causing the structure change in integrin so that it is activated on the extracellular side
-Both pip2 and pip3 activation is proposed
-Bidirectional
Cell-adherence junctions (4)
1) Anchoring junctions (desosomes)
- anchor the cells to each other and then anchor the cells to the ECM
2) Occluding junctions (tight junctions)
-ensure nothing leaks through the epithelial layer, found generally along apical side
3) Channel-forming junctions (Gap junctions)
-usually closer to basal side, allow transfer of small molecules between cells
4) Signal- relaying junctions (Notch Delta)
- membrane bound ligand on one cell that interacts with membrane bound receptor on another cell, transmits signal to both
Cadherins mediate
adherens junctions
Adherens junctions link
actin cytoskeleton between 2 cells
Linking the cytoskeleton to the ECM is always done at the ____ side of an epithelial cell: actin through ________ and IF through __________
basal: integrin signalling, hemidesosomes
Development of a neural tube what part develops the peripheral nervous system
Neural crest on top
Ectoderm to neural tube
-Start with ectoderm that has high expression of E-Cadherin
-This layer infolds which develops the neural tube
-This causes a shift to a high expression of N-cadherin and down regulate E-cadherin
-The junctions of the fold have a different expression – up regulation of cadherin 6B causing these folds to actually fuse
-What you get is the neural tube closing with separated cells above and cells that can migrate, differentiate and change their expression to cadherin 7
B-catenin involvement with cadherins
B-catenin involved with cell junction AND WNT SIGNALLING: Wnt activates genes involved with cadherins involving cadherins themselves
Collagens are extremely rich in …
A. alanine and valine.
B. glycine and proline.
C. lysine and arginine.
D. serine and threonine.
E. tyrosine and phenylalanine.
B
What is the main function of fibroblast cells?
A. Connect the cell to the ECM
B. Secreting components of the ECM
C. Help disperse the mechanical stress
D. Connect the basal lamina to the ECM
E. Activate mast cells
B
What are the two essential components of the basal lamina?
A. Type IV collagen and Laminin γ-1
B. Type I Collagen and Fibronectin
C. Elastin and Type IV Collagen
D. Laminin and Perlecan
E. Elastin and Laminin
A
2 types of short segments elastin molecule is made up of
1) Hydrophobic segments - responsible for elastic properties
2) Alanine and lysine rich alpha-helical segments
Similarities and diferences between collagen and elastin
SAME:
-both rich in proline and glycine
DIFFERENT:
-only collagen is glycosylated
-elastin contains hydroxyproline NOT hydroxylysine
Laminin and collagen molecule
LAMININ-1:
-Large, flexible protein composed of 3 peptide chains (alpha, beta, gamma)
COLLAGEN:
-Long, stiff triple stranded helix , 3 alpha chains wound around eachother
-rich in glycine (EVERY 3rd A.A)
Integrins are
Transmembrane heterodimers that can link to cytoskeleton
Cadheins only found in
Animals
Particular type of IF attached to desosome in each cell type
keratin filaments in most epithelial cells and desmin filaments in heart muscle cells
