Name and explain the cell junctions in vertebrate epithelia.
From apical to basal:
tight junctions: seal gap between epithelial cells
adherens junctions: connect actin filament bundles of one cell with that in the next cell
desmosome: connect intermediate filaments in one cell with those in the next cell
gap junctions (channel forming junctions): allows passage of small water-soluble molecules from cell to cell
actin linked cell-matrix junction: anchors actin filaments in cell to extracellular matrix
hemidesmosome: anchors intermediate filaments of the cell to ecm
Desmosomes and adherence junctions: What do they have in common, what are the differences?
Common:
cell-cell adherens via Cadherins (but not the same ones)
Ca2+ dependent
Differences:
Anchorage: desmosomes linked to intermediate filaments in the cell, adherens junctions with actin
structure of connectors:
Desmosome: IF - desmoplakin - plakoglobin / plakophilin —-> [through membrane] —> desmoglein / desmocollin (=non classical cadherins)
AJ: actin - vinculin (tension) - alpha/beta catenin - p120 catenin - classical cadherin [E-Cad] [trough membrane]
function:
Desmosome: mechanical strength, protection from ripping
AJ: epithelial folding, tubes, pits, spheres / remodelling, Adherence junctions respond to forces generated by the actin cytoskeleton (myosin II pull too)
What are the tight junction proteins? Whats their purpose?
claudin and occludin
purpuse: sealing the intercellular space and apical / basal polarity
The Par3/Par6/aPKC complex assembles at tight junctions and initiates the formation of a basal lamina on the opposite end of the cell
Name key characteristics of the basal lamina.
• thin, tough, flexible sheet of extracellular matrix molecules
• 40-120 nm thick
• below all epithelia
• surrounds muscle, fat and Schwann cells
• multiple functions: structural stability, filtration; influences cell metabolism, cell survival, cell proliferation, cell differentiation; organizes protein distribution in the plasma membrane, highway for cell migration
The basal lamina is synthesized by the cells on each side of it.
Name the main components of the basal lamina.
Collagen (type IV) (gives tensile strengh)
laminin = main organizere (3 intercoiled chains (a/ß/y)
perlecan
nidogen (additional connector of collagen and laminin)
integrins (through the plasma membrane to anchor the cells) (connect to laminin)
Explain how epithelial cells are connected to extracellular matrix.
actin linked cell matrix adherens
via activated integrins (ligand binding)
laminin - integrin (a/ß subunit) - kindlin (bud at end) - talin - vinculin - actin
hemidesmosomes
clusters for strong adherens
collagen XII and collagen I / II under basal lamina with collagen IV - laminin - integrin + collagen 17 - plectin + bp230 - intermediate filaments (kreatin)
Desmosomes and hemidesmosome: What do they have in common, what are the differences?
linked to intermediate filaments
give the cell mechanical strengh
Difference:
adhesion molecule —> cadherins vs. integrins
cell-cell vs. cell-matrix adhesion
One of the components of adherens junctions has a second function in a signaling pathway that is important during embryonic development and tumorigenesis. Please name this component and briefly explain its function in signaling.
ß-catenin is a component of the canonical WNT pathway, upon activation the ß-catenin translocates to the nucleus and associates with Lef/Tcf proteins to form transcriptional activator
Cell adhesion molecules were originally identified using antibodies raised against cell-surface components to block cell aggregation. In the adhesion-blocking assays, the researchers found it necessary to use antibody fragments, each with a single binding site (so-called Fab fragments), rather than intact IgG antibodies, which are Y-shaped molecules with two identical binding sites. The Fab fragments were generated by digesting the IgG antibodies with papain, a protease, to separate the two binding sites (Figure Q19–1). Why do you suppose it was necessary to use Fab fragments to block cell aggregation?
The use of Fab fragments in cell aggregation assays allows for increased specificity, reduced potential for crosslinking (IgG has two connected binding sites), improved steric hindrance (smaller size), and enhanced flexibility (small and better accessibility) in blocking the interactions between cell adhesion molecules.
Which statements are true? Explain why or why not.
19–1 Given the numerous processes inside cells that are regulated by changes in Ca2+ concentration, it seems likely that Ca2+-dependent cell–cell adhesions are also regulated by changes in Ca2+ concentration.
True. Changes in intracellular Ca2+ concentration play a crucial role in regulating various cellular processes, including cell–cell adhesions. For example, in cadherin-based cell–cell adhesions, Ca2+ is involved in modulating the binding affinity of cadherin molecules. When Ca2+ levels are low, cadherins do not bind strongly, allowing cells to detach. Increased Ca2+ levels strengthen cadherin binding, promoting cell–cell adhesion.
19–2 Tight junctions perform two distinct functions: they seal the space between cells to restrict paracellular flow and they fence off plasma membrane domains to prevent the mixing of apical and basolateral membrane proteins.
True. Tight junctions are complex structures that serve as both a barrier to paracellular transport (preventing the passage of ions and molecules between cells) and as a boundary between apical and basolateral membrane domains in epithelial cells. This helps maintain cell polarity and the separation of distinct membrane protein populations.
19–3 The elasticity of elastin derives from its high content of α helices, which act as molecular springs.
False. Elastin's elasticity arises from a unique structure composed of cross-linked tropoelastin units, not α helices. Elastin is rich in glycine and proline, and it forms a rubber-like protein that provides elasticity to tissues like skin, blood vessels, and lungs.
19–4 Integrins can convert mechanical signals into intracellular molecular signals.
True. Integrins are cell surface receptors that link the extracellular matrix to the cytoskeleton. They can transmit signals bidirectionally, converting mechanical signals from the extracellular environment into intracellular signaling events. This process, known as mechanotransduction, is essential for various cellular functions, including cell adhesion, migration, and response to mechanical forces in the microenvironment.
Structures of
adherens junctions
desmosomes
actin linked cell-matrix junctions
adherens junction
desmosome
actin linked cell-matrix junction
hemidesmosome
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