Biology 211 Final Exam 2

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How Twist inhibits cells from behaving like epithelial cells?

A transcription factor called Twist, which regulates the expression of E-cadherin. When E-cadherin is expressed, cells have an epithelial character. Twist inhibits the expression of E-cadherin. As a result, when Twist is expressed/active, it tends to promote the transition to mesenchymal cells.

How collagen chains are modified and ultimately assembled into fibrils?

A typical collagen molecule has a triple strand helical structure (right). In this structure, three collagen α-chains (left) wrap around each other. Collagen proteins have a large number of proline and glycine amino acids. The structure of proline favors the formation of a helix. Glycine is the amino acid that has the smallest side chain. As a result, but having it regularly spaced to be every third residue in the protein, it packs in towards the center of the triple helical structure, allowing for tight packing of the three strands. Many of the prolines and lysines in collagen are hydroxylated after the collagen has been synthesized. These hydroxyl groups are thought to stabilize the triple helix. The enzyme that adds the hydroxyl group requires vitamin C as a cofactor.

What are the basic features of a typical collagen molecule?

A typical collagen molecule has a triple strand helical structure (right). In this structure, three collagen α-chains (left) wrap around each other. Collagen proteins have a large number of proline and glycine amino acids. The structure of proline favors the formation of a helix. Glycine is the amino acid that has the smallest side chain. As a result, but having it regularly spaced to be every third residue in the protein, it packs in towards the center of the triple helical structure, allowing for tight packing of the three strands. Many of the prolines and lysines in collagen are hydroxylated after the collagen has been synthesized. These hydroxyl groups are thought to stabilize the triple helix. The enzyme that adds the hydroxyl group requires vitamin C as a cofactor.

That cell adhesion receptors form important connections to the cytoskeleton, and can cross-talk to signaling pathways and why that is important to their function?

Adhesion junctions are attached to the cytoskeleton in order to coordinate higher order movement in cells and to anchor the cell. To allow for coordinated behavior of tissues. Cells need to have mechanisms to adhere to one another or to extracellular materials in order to have organization to allow for development of tissues and coordination of function, as well as an establishment of order to sort cells during development and cell connections.

What are the functions and composition of adherens junctions, desmosomes, hemidesmosomes, tight junctions, septate junctions, gap junctions and plasmodesmata?

Anchoring junctions in animal cells include desmosomes and adherens junctions. Demosomes attach to intermediate filaments in the cytoplasm, while adherens junctions attach to actin filaments. There are two types of anchoring junctions that are involved in cell-matrix adhesions: hemidesmosomes and actin-linked cell-matrix adhesion. Hemidesmosomes involve integrin proteins that can bind to extracellular matrix proteins outside of the cell, and intermediate filaments inside of the cell. Actin-linked cell-matrix adhesions involve integrin proteins that can bind to extracellular matrix proteins outside of the cell and actin filaments inside of the cell. Tight junctions prevent movement of membrane proteins from the apical membrane to the basolateral membrane.

Why there are so many different cadherin family members, and how cadherins are involved in organizing tissues?

Cadherins bind to other cadherins of the same type. What this allows is for cells to identify and form sheets of cells with other cells of the same type. This sorting out of tissues has been attributed to the cadherins. Cadherins have greater affinity for cadherins of the same type. As a result, cells with the same types of cadherins stick together - forming a layer of tissue. In fact, cadherin expression is one of the things that is regulated during development to allow for the development of distinct tissues.

What are the general types of junctions that can occur between cells or between cells and matrix, and their basic functions?

Cell-cell adhesion is accomplished by interactions in which molecules on the surface of one cell interact with molecules of the same type on the surface of another cell. There are four main classes of cell-cell adhesion junctions: Anchoring junctions, occluding junctions, channel-forming junctions and signal-relaying junctions. Anchoring junctions are junctions that anchor cells to one another through the use of transmembrane proteins that can interact with each other extracellularly, and with the cytoskeleton intracellularly. Anchoring junctions in animal cells include desmosomes and adherens junctions. Demosomes attach to intermediate filaments in the cytoplasm, while adherens junctions attach to actin filaments. Occluding junctions form a selectively permeable barrier between cells to regulate what can pass between cells. In vertebrates, these occluding junctions include the tight junctions, while in invertebrates, these are the septate junctions. Channel-forming junctions link the cytoplasms of one cell to another. In animal cells, the channel-forming junctions are gap junctions, while in plant cells these are plasmodesmata. Signal-relaying junctions are synapses. Synapses provide a mechanism to relay a signal from one cell to another cell.

Why cells in connective tissues need to have the ability to synthesize and degrade ECM?

ECM can be degraded to allow for turnover and remodeling of matrix. This can allow the matrix to change in response to stresses. In order for cells in the matrix to be able to make new cells, they need to be able to degrade matrix to make space to grow and divide. Cells in the matrix also have to be able to degrade the matrix in able to move through it. If cells in connective tissues, such as fibroblasts cannot digest ECM, they will not be able to effectively move, nor to divide.

What is the composition and function of the ECM?

ECM is a series of macromolecules that underlie or surround cells. It is made up of many different types of molecules. The types and ways that these molecules are organized can give rise to a variety of forms. For example, it can be calcified to form bone or teeth. It can contain other substances to form tendons or the cornea of the eye. It can form the material that underlies epithelial cells or surrounds other cell types. The ECM provides structural support and tensile strength to cells. It provides a substrate for cell adhesion and cell migration. It can regulate cellular behavior in a variety of ways. Importantly, ECM is not cellular, but it is made of cells. Instead, ECM is made up of proteins and sugars.

How the ECM in different tissues or organisms might be different?

ECM is a series of macromolecules that underlie or surround cells. It is made up of many different types of molecules. The types and ways that these molecules are organized can give rise to a variety of forms. For example, it can be calcified to form bone or teeth. It can contain other substances to form tendons or the cornea of the eye. It can form the material that underlies epithelial cells or surrounds other cell types. It also makes up the cell wall in plants. The ECM provides structural support and tensile strength to cells. It provides a substrate for cell adhesion and cell migration. It can regulate cellular behavior in a variety of ways. Importantly, ECM is not cellular, but it is made of cells. Instead, ECM is made up of proteins and sugars.

Why epithelial cells are polar, and how that polarity is established?

Epithelial cells are organized such that they are anchored to an extracellular matrix structure called the basal lamina on one side, the basal or basolateral side. On the other, apical, side, epithelial cells are free from attachment to the extracellular matrix. The apical side is usually bathed in some sort of extracellular fluid. These cells are considered to be polarized, which means that they have an asymmetrical organization. Another type of polarized cell is a neuron - with dendrites on one end and a long axon on the other end. Cell polarity is established by epithelial cells in response to the existence of the basal lamina, and polarized neighboring cells. Cell-cell and cell-matrix adhesions allow a cell to sense its environment and establish polarity in relation to these other structures. This polarity is further maintained by tight junctions, which, in addition to serving as selective permeability barriers that prevent the free movement of materials between cells, also prevent the movement of membrane proteins between the apical and basolateral domains of the plasma membrane.

How physical attachment differs in epithelial versus connective tissue, in general?

Epithelial tissue is a type of animal tissue that lines the surfaces of structures throughout the body. This is important in creating compartments in the body. For example, skin is an epithelial layer and so is the lining of the gastrointestinal tract. Because these structures are exposed to the environment, these cells are usually organized so that they are tightly adhered to one another in order to regulate what moves between them, and to ensure that these cells do not easily become detached upon interacting with the environment. The connective tissue layer contains cells, including fibroblasts and macrophages, which can move through the connective tissue layer. This layer also contains extensive extracellular matrix materials. While the cells in the epithelium need to stay in place within the tissue, for the most part, to maintain tissue function, cells in the connective tissue can move. As a result, the types of connections that cells make within the connective tissue are different from the types of connections that cells make in the epithelium. In the epithelium, cells tend to have extensive cell-cell interactions, as well as cell-matrix interactions. In connective tissue, persistent cell-cell interactions aren't as important to cells like fibroblasts. These cells will likely have cell-matrix contacts, which can be dynamically regulated.

What the basal lamina is, the basic composition of the basal lamina, and why it is important in tissue organization?

The basal lamina is a thin and flexible sheet of extracellular matrix that is found under all epithelial cell layers in multicellular animals. Basal lamina also surrounds some nonepithelial cells such as muscle cells, fat cells and Schwann cells, which are the cells that wrap around axons and form myelin. The role of the basal lamina is to separate cells from the underlying or surrounding connective tissue. It also connects epithelial cells to that connective tissue. Basal lamina can serve as a filter, provide structural and mechanical roles, help to determine cell polarity, play roles in metabolism, promote cell survival, proliferation and differentiation and also provide a substrate for cell migration. The basal lamina is composed of a variety of different factors in different tissues. However, common in all tissues are laminin, type IV collagen, nidogen and perlecan. Laminin forms a network of proteins into an orderly sheet. This organizes the basal lamina. Type IV collagen is a ropelike polymer that forms a flexible network, which provides strength to the basal lamina. Type IV collagen is connected to laminin by nidogen, which is a glycoprotein, and perlecan, which is a proteoglycan.

How can jap junctions be regulated?

Transport through both plasmodesmata and gap junctions can be regulated. Here we will focus on regulation of movement of materials through gap junctions. Gap junctions can open and close. Decrease in cytosolic pH or an increase in cytosolic calcium to high levels leads to a rapid closing of the channel. Though it is still unclear why a decrease in cytosolic pH leads to the closing of gap junctions, it is clear why an increase in calcium leads these channels to close. Cytosolic calcium levels are typically maintained at very low levels, as we have discussed throughout this course. Calcium levels tend to increase when there is damage to the plasma membrane or other structures. As a result, it is thought that gap junctions close when calcium levels rise to protect neighboring cells. When calcium levels rise in a cell, the gap junctions close to ensure that neighboring cells are not affected by whatever is damaging the cell that has increasing calcium concentrations.

Why tight junctions are important in epithelial tissues?

Typically, tight junctions selectively prevent the movement of materials between epithelial cells to regulate what substances can enter a tissue layer. Tight junctions also prevent the movement of materials within the plasma membrane, thus establishing an apical region (the top part of the cell above the tight junction layer), and a basal or basolateral region (everything below the tight junctions).

What are the types of cells that make up ECM?

• GAGs (glycosaminoglycans): are unbranched polysaccharide chains composed of repeating disaccharides. They attract water, and therefore they form a hydrated gel that protein fibers can weave through. • Proteoglycans: are a protein core (one of about 20 different types) attached to GAGs. Each protein core can attach to a variable number of GAGs. These are large proteins. They can bind to other proteins and perform a variety of functions, such as regulating secreted proteins, serving as signaling co-factors, and serving as a reservoir for secreted factors. • Fibrous proteins: Fibrous proteins are also an important component of ECM. The major proteins of the ECM are collagens, which make up 25% of the protein mass of animals. They are a major component of bone and skin. There are many different forms of collagen. Laminin is an important component of the basal lamina, which I will discuss further on a subsequent slide. Elastin provides elasticity to tissues that contain it. Fibronectin is a large glycoprotein that can help with cell-matrix interactions. o Collagens o Laminin o Elastin o Fibronectin

What are selectins and integrins?

• Selectins are proteins that are found on cells in the bloodstream, which allow for transient cell-cell adhesions. They are primarily important in endothelial cells, platelets and white blood cells. Selectins are proteins that bind to carbohydrates that are found on white blood cells and platelets. • Integrin is unique compared to other transmembrane proteins involved in cell adhesion because it has two conformational states, an active conformation that can actively bind to binding partners and an inactive conformation. In other words, binding of integrin to its binding partners is regulated. The inactive integrin (see left) has alpha and beta chains that are bound to each other, leading to a conformation in which the extracellular portions are folded in and cannot bind tightly to ligand. The active integrin (see right) has alpha and beta chains that are dissociated, leading to a conformation in which the extracellular portions are stretched out and can bind strongly to ligand. integrin can be activated either by ligand binding outside of the cell, or by talin binding inside of the cell. The inside-out activation pathway can be stimulated by signaling pathways that promote talin binding to integrin. Ultimately, integrin activation can allow binding of cells to extracellular matrix proteins.

What transmembrane adhesion protein is relevant for each type of junction, and what cytoskeletal element these proteins interact with in the cytoplasm?

•Tight junctions - claudins and occludins •Gap junctions - connexins •Plasmodesmata - does not make use of proteins to connect the cells - rather these are places where cell wall has not been deposited so the two cells remain connected •Both adherens junctions and desmosomes make use of cadherin proteins, and both of the cell-matrix anchoring junctions make use of integrins.


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