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Lecture 3

Lecture 3 - Prof. Harris - cell connections.pdf

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Maurice Ringuette

Lecture 3 - Prof. Harris October 29, 2015:48 AM We are talking about how individual cells can be assembled into alrger tissues or whole animals. Look at the single cell: This is really small. Fragile. Has a lipid bilayer. PM surrounding it. Cytoskelton within i. How does this cell form that mouse? And give the physical integrity it need? One answer to the Q is that cells are orgnized into different cell types. These cells are connected to on another: forms a layers of cells: and behoind these they have cytoskelton netwroks we talked: these cytoskeltons are conencted to cell adhesion complexes which connects to its neighbor which also has another adhesion complex If you look at this cellthere is a hige protein imteraction complex: bl filament to adhesion complex --> blue filament to black adhesion complex --> etc This is spanning the nentire tissue and it can support the whole tissue This is beneath the eoithelial tissue is the conective tissue. This is where the immune cells crawl through to helo protece the cell from foreign substances. Physical structure of the connective tissueis made form ECM. These are polymers of sugar found outside the cell. In a similar way creates There is a huge structure of cells which resists complressoion and pulling foces. By having protein interac ton through this Epi. Cells it gives a larger physical siupport to tissues that make up the body These epithelial tissues within them the cells are directly cononected and they have the minimum ECM beneath them. A strip of yellow layer. Connected tissues we have individual cells and they are disperesed within the ECM. BIO230 Page 1 We focus on epithelial structure and why its important. Epithelia forms barriers which is critical for our organ structure and function. For the skin speration is between the external and internal environement Organs: the lumen and cell You can imagine your own body startig from one point and to antoher point and ask what tisse structures do you pass. You pass skin --> epithelial clls --> conective tissu (bones, tissue, ECM, tendons) --> epithelium (forms our gut ) --> lumen of our gut. You can see this in the human abdomen. Epithelium is forming the organ and skin, and between the epithelium its the ECM BIO230 Page 2 There are multiple junctions in epithelia which gives them structural and functional properties 1. Anchoring jnctions: can connect the ECM and the cytoskeleton and actin networks inside the cell. These junctions are formed from, integrins. Gives a tight connection to the ECM. a. Cell cell anchoring jucntions: receptors passing between, interactin gwith the cell on the other side. Inside you have connections to the cytoskelton/actin netwroks. b. Adherenc: desmosomes. Both of these are based on adherence receptors These connect the epithelium cells together. There are occluding juntions : seals the spaces between te epithelium cells. Forms a strong barrier form one side if the epithelium sheet to the other. Gap junctions: Forms channels between the cells. Allows the cell to communicate between one another and share resources. Small molecules can pass through these to communicare or share resources. Anchroing junctions Anchoring junctions between epithelium cells. Imagine you are standing inside the single epithelium cell and you can see a band of actin on the cytoplasmic face of the PM. The red filamnets are actin filaments which are connected to the adhesion receptors which reach out and interacts with the adhesion recptors oon the oppostie side. Analogy: brick. Cytoskelton gives the brick a strucyture. The adhesion cmolex between the bricks can act like mortor to start creating the bur=icks togethr to form the 2D…? EM of the epithelium: yellow highlighted parts: plasma mebrane from one cell and the PM from the othere there are space and very specific distance between them.that is because there are specific receptors interacting with them. Inside you can see the cytoskelton which supports the junction Single epithelium cell. BIO230 Page 3 The way that caherens do the functio is by forming clusters. There is one single cadherin protein which reach out ad interacts with cadherin moelcules in the other cell in clusters. There are individual molecules adding up to a large force. The cadherin molecules reach out and interact with each other in 2 main ways. One is that they reach out through the extra celular space and binds homophillically. --> like with like. If it was E cadherin it binds to E cadherin on the other sie One single cadherin protein. Reaches out and interacts with the opposite cell. There are two main ways 1 they reach out and interact with each other homophilically: like with like. E cadherin binds to e cadherin on the other side. Homophillic interactions Imagine the region from crystal structure there There is a specific Amino acid sequence which loops and pokes into the hole on the Extracellular oppostie sice and reaches out and mediates the molecule mechains, receptor The cytoplasmic side there are adapter proteins which links the receptors to the actin cytoskeleton. Overall startegy for the anchring junction is similar for the organizstion seen in integrins: we have an extracellular receptor which binds to something on the outside and adpators which links it to the cytoskelton within BIO230 Page 4 Why are adherence juncitons importatn? Adherence junctions can be regulated very specifically. The brick and mortar analogy falls apart. We can see how this sheet of cells can move dynamically in the early dvelopment of an embryo. Look how it still remains connected with one another and the sheet remains intact. That’s when the brick wall falls apart because the bricks will fall apart. These tissues can be sculpted during development. In the next embryuo there is a mutation in one of the key adherence junctions The movement is attempted, suddenly lose contact with one another and looses its intergrity and idsintergrates (next slide) BIO230 Page 5 This same role can be seen in adult tissesu and cancer tisseus. The epithelial of normal cell is well organized. In caner tissued there is an disorganziation like what we saw in the embryo. Loss is epithelium is a hallmark of cancer. Cadherins are important for holding the structure together and suppressing the progression of cancer. Disorganized. Those are number of ways why epithelial structure is important. The polarity of ept. Cells It means that one side of the cell is different from the other side. The organ lumen or the animal surface Underlying tissue When I use polarity it means differences between one side of the strucure is different from the other. There are two main parts of the PM of the cell which is differnet. We have an apical surface, and this will either face the lumen of the organ or the outside of the body. The basl surface faces the underlying tissue which is the connective tissue we were talking about. Connective tissue is always connected to the basla surface and the other side faces the lumen of an organ or the outside of the body BIO230 Page 6 Epithelial barriers are not absolute, but they can be regulated., the cell controls them because of its polarity. Epithelial polarity is used to gather sugar from the gut in this: Gathering sugar from the gut. Apical surface faces the lumen where it has glucose from digested food. You have digestive environement adna cidic studd. The body wants to gather the glucose but not the other parts. So one critical component is the tight junctions formed between the apical embrane and the basolateral meembrane. They seal from any material from passing in between the cells. So that forces transport to go THROUGH THE CELL. So there are plasmam mebrane channel which will only accept glucose and reject other stuff from the gut. So there is a
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