Module 8 - Cell Adhesion Flashcards
1
Q
multicellularity
A
- multicellular organisms develop from a single fertilized egg
- development requires reiterated mitotic divisions to produce multiple cells, cell differentiation that defines tissue specific patterns of gene expression and signalling between cells
- also requires that cells are able to maintain connections
2
Q
embryogenesis
A
- during embryogenesis, can. see. the formation of the inner cell mass which forms the early embryo
- as the # of cells increases, they separate into 1/3 germ layers. endoderm, ectoderm and mesoderm
- cells throughout the developing embryo must establish and maintain connections
3
Q
cell reorganization and adherance in sponges
A
- ability of cells to reorganize and adhere to one another was demonstrated in 1907 in sponges
- individual cells of these multicellular organisms were separated apart using a fine mesh and then mixed together
- the cells from the same species were able to recognize and associated back. together, while cells from the different species did not associated
4
Q
embryonic cell association
A
- is cell-specific
- similar experiment to sponges was performed with frogs in 1950
- took cells from 2 different germ layers during development and separated apart individual cells
- when these 2 different types of cells were mixed together, cells from like tissues recognized one another and associated
- associations even mimicked the organization seen in the original embryo
- cells require a collection of. transmembrane proteins that span the cell membrane called cell adhesion molecules (CAMS) that allow them to recognize and contact each other and stay together during embryogenesis
- after aggregation, cells form specialized cell junctions that stabilize cell-cell interactions and facilitate communication between adjacent cells
5
Q
epithelial cell connections
A
- connect to one another along their lateral surfaces. to form epithelial sheets that line body cavities
- epithelial sheets form. the inner lining of the digestive system and the outer layer of the skin
- cells have distinct apical and basal surfaces of the cell and have distinct structure and function
- basal surface is anchored to the extracellular structures that provide an underlying structure to the sheet of cells and include the basal lamina or basement membrane
- adhesion complexes called hemidesmosomes to connect cells to the extracellular matrix
- the apical surface of this intestinal epithelial sheet is organized into microvilli that face the interior of the intestine
6
Q
types junctions in epithelial cells
A
tight junctions adherens junctions desmosomes hemidesmosomes gap junctions
7
Q
tight junctions
A
- also known as zonula occludens
- connect adjacent epithelial cells just below the apical surface, completely sealing off the space between the cells
- this prevents fluid movement across the layer of cells, restricting the diffusion of small molecules and the leakage of digestive enzymes
- linear arrays of proteins called occludin and claudin are closely arranged between neighbouring cells
- band formed between the cells prevents diffusion of membrane portions from apical to basolateral regions of the plasma membrane
- it also completely prevents the diffusion of molecules in the extracellular space between the cells
8
Q
freeze fracturing for tight junctions
A
- in freeze fracturing, cells are instantly. frozen in liquid nitrogen and then broken apart
- fracture is irregular, but occurs at points of weakness such as on the lateral surface between neighbouring cells, allows researchers to see the network created by the tight junctions
- lines are the linear array of tight junction proteins that criss cross the lateral surface f the cells
- tight junction is celarly not a single junction, but an accumulation of structures that form a complete band between the cells
9
Q
gap junctions
A
-directly link the cytosol of one cell to the cytosol of the adjacent cell
-this integrates the metabolic activities of all cells in a tissue by allowing the exchange of ions and small molecules between cells, including secondary messengers such as cAMP and calcium
each channel allows the free diffusion of up to about 1 kDA in size through the channel
-gap junctions allow the rapid. coordination of cardiac muscle. contraction and uterine muscle contractions
-the hormonal stimulation of. one cell can lead to a response shared by many cells through the diffusion of the secondary messengers directly through the flow of the cytosol from one cell to the next
10
Q
connexion channel
A
- found in groups to form the gap junctions
- a gap junction between. neighbouring. cells where the have the additional effect of pinching together the cell membranes and holding the cells together, however, within the extracellular. space, molecules can diffuse around the junctions
11
Q
plasmodesmata
A
- structures in plant cells that perform a similar function to gap junctions found in animal cells
- are important to the structure and function of the phloem found in flowering plants
- phloem carries nutrients, including products of photosynthesis such as sucrose, from the leaves to the rest of the plant
- the cells of the phloem called sieve tube elements are connected by modified and enlarged plasmodesmata that form. the sieve tube plate
- while the sieve tube elements are metabolically inactive, specialized cells called companion cells are closely associated with their development and function
- communication through plasmodesmata involves the trafficking of. informational macromolecules such as transcription factors, gene transcripts and small RNAs
- unfortunately, viral pathogens exploit these channels for intercellular spread
12
Q
companion cells
A
- provide ATP, proteins and other substances to the sieve tube elements
- are connected the cells of the phloem by plasmodesmata
- channels of the plasmodesmata that must span not only the two cell membranes, but also the cell walls
13
Q
phloem
A
-acts as a circulatory system for the plant, carrying sucrose from source cells (photosynthetically active leaf cell) to the rest of the plant
14
Q
anchoring junctions
A
- include adherence junctions, desmosomes and hemidesmosomes
- these are distinguished from. other junctions by their association with the cytoskeleton in particular actin filaments
- adheren junctions connect the actin cytoskeleton between neighbouring cells
15
Q
desmosomes
A
-link 2 cells together
16
Q
hemidesmosomes
A
-attach one cell to the extracellular matrix
17
Q
CAMs
A
cell adhesion molecules making up the adherens junctions fall into 4 major families
1) cadherins
2) ig-superfamily
3) integrins
4) selectins
- some are responsible for the association of similar cells (homophilic interactions), other predominantly connect different cells together (heterophilic interactions)
18
Q
cadherins
A
- critical cell adhesion molecules of the adherens junctions
- calcium-dependent CAMs that mediate homophilic interactions
- 3 major classes
1) E-cadherin (epithelial)
2) N-cadherin (neural)
3) P-cadherin (placental) - these junctions mediate epithelial cell-cell adhesion hear the apical surface of the cells, just below the tight junctions
- adhesion is mediated by multiprotein complexes involving the transmembrane cadherins, but also cytosolic cofactors, the catenins that anchor cadherin to the actin cytoskeleton
19
Q
aggregation of epithelial cells with cadherins
A
- under standard cell culture conditions, epithelial cells do not aggregate into sheets
- introduction of a gene that expresses E-cadherin (an added transgene) into these cells results in their aggregation into epithelial-like clumps
- E-cadherin mediates calcium-dependent adhesion of epithelial cells, illustrated by aggregation of the cells in the presence of calcium but not in the absence of calciu
20
Q
cadherins and cell differentiation
A
- E-cadherin mediates tissue-specific adhesive connections in cultured epithelial cells
- an E-cadherin gene fused to GFP was introduced into cultured cells. cells were then mixed together in a calcium-containing medium and the distribution of fluorescent E-cadherin was visualized over time
- the maintenance of adhesion and the formation of functions is highlighted by the accumulation of GFP-E-cadherin at the surface of neighbouring cells
- cells adhere only to other cells expressing the same. cadherin as these are homophilic interactions
21
Q
Temporary cell-cell associations
A
- cell adhesion is important for establishing and maintaining cell connections, there are examples where cell function requires transient or temporary associations that are established but then broken again
- examples include connections that allow cells to migrate across an extracellular surface and the migration of cells during embryogenesis
22
Q
leukocytes movement
A
another temporary cell adhesion response
-movement of leukocytes in response to local viral or bacterial infections or traumatic injury
the movement. out of the blood vessel depends upon a precise sequence of adhesive interactions which together are called extravasation
-endothelial cells are specialized epithelial cells that form the walls of the BVs
-adhesion of these cells prevents the leakage of cells out of the BVs
-normally leukocytes are moving quickly with the RBC in flow of blood through the BVs
-the leukocytes must be able to establish temporary connections with the endothelial cells in order to mediate the process of extravasation and get to the site of infection
23
Q
types of leukocytes
A
granulocytes: neutrophils, eosinophils and basophils
monocytes
lymphocytes: NK cells and T and B cells
24
Q
granulocytes
A
target pathogens
eosinophils and basophils dont undergo extravasation
25
neutrophils
most numerous, target primarily bacterial infections and are one of the first cells to respond to trauma
undergo the process of extravasation
26
monocytes
differentiate into macrophages that engulf invading bacteria or dead/damaged cells through phagocytosis
-cells are also capable of extravasation
27
NK cells
natural killer cells
lyse vitally infected cells and tumor cells
can undergo extravasation
28
T and B cells
produce antibodies as part of the immune response
| can undergo extravasation
29
extravasation
- 5 step process that is initiated by a signal that is created by an infection
1) capture - a transient association between the neutrophil and the apical surface of an endothelial cell within the endothelial wall. neutrophils are still pushed by the flow of blood through the vessel, but the movement is slower
2) rolling - instead, cells are rolling along the surface of the endothelial. cells
3) slow-rolling - rolling slows as the number of associations between. the neutrophil and the endothelial cell increases
4) firm adhesion - firm adhesion is the stronger attachment of the neutrophil with the endothelial cells
5) transmigration - this is accompanied by dramatic changes in cell function and structure, that allow them to break the connection between endothelial cells and migrate along the surface of the cells into space outside of the BV in a process called transmigration
- at the site of infection, swelling occurs as a result of the escape of blood plasma in addition to the transmigration of various leukocytes
30
capture
- the first step is the signal from the site of infection that triggers capture of the neutrophil
- this is mediated through cytokines released at the sites of infection
- cytokines change the behaviour of the endothelial cells that make up the BV wall
ex. cytokine TNF alpha = receptor on the basal surface of the endothelial cell receives the signal and triggers the release of selectins on the apical surface of the cells
- neutrophil in the resting state means that it is flowing freely through the BV, in the endothelial cell, the P-selectins are held in. regulated secretory vesicles
- upon reviewing the cytokine signal, the secretory vesicles transport the P-selectin to the surface of the endothelial cells that allows the P-selectin to interact with their ligands, a glycoprotein on the surface of the leukocyte
31
rolling movement
- the adhesion of the neutrophil to the endothelial cells slows neutrophil movement
- the movement of neutrophils as they are pushed over the surface of the endothelial cells while establishing and losing transient connections is called rolling
32
slow rolling
- the density of selectins on the surface of the endothelial cell increases as the neutrophil gets closer to the site of infection
- many endothelial cells at the site of infection are slow displaying both p-selectin and E-selectin
- the increasing number of associations between selections and the ligand on the neutrophils further slows movement
33
firm adhesion or tight binding
- slow rolling allows new interactions between the endothelial cells and the neutrophil
- a membrane-anchored signal or cytokine on the endothelial cell called PAF (platelet-activating factor) can now interact with the transmembrane receptor on the neutrophil called the PAF receptor
- ex. of neutrophil cytokine receptors include CXCR1 and CXCR2 which are members of the GPCR family of receptors
- ligand binding to the PAF receptor can only occur if the cells are undergoing slow rolling
- activation of the PAF receptor by ligand binding initiates a signalling transduction pathway inside the neutrophil
- there are many. cellular responses in the neutrophil that includes changes in patterns of gene expression. and activation. of yet another cel adhesion molecule
- the activation of integrin, allows it to interact with its ligand, the ICAMs and further slow movement
34
activation of integrins
- a ribbon diagram of the dimeric integrin in its inactive form has the propeller and beta-A domain folded down
- since these form the ligand-binding domain, the integrin cannot recognize its signal
- switch to the active conformation occurs as a result of PAF signalling
- the integrin can now bind to its ligand on the endothelial cells, the ICAMs
- the association between integrins and their ligands is stronger than the selectin interactions
- this further slows movement and establishes firm adhesion
- activation of integrins also signals more changes in neutrophil behaviour
- this includes a reorganization of the actin cytoskeleton to allow cell migration
35
transmigration
- process by which the neutrophil no longer moving with the flow of blood, has stopped at the site of infection and is. able to migrate by crawling between the endothelial cells
- the connections between the endothelial cells have been broken by enzymes produced by the transmigration neutrophil
36
progressive acti vation of extravaasation
```
selectins = activated first to mediate capture, rolling and slow rolling
integring = signalling pathways then activate integrins to mediate firm adhesions and allow transmigration to occur
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