unit 2 week 3 pt 2 Flashcards
How do cells organize themselves within developing organs?
The complex three-dimensional arrangements of cells in developing organs are thought to depend on selective interactions between cells of the same type and different types. Studies of organoids in vitro help researchers understand these processes.
How did early experiments explore cell-cell recognition and adhesion?
Early experiments involved dissociating developing organs from embryos and placing the single cells in culture. Cells from different organs would initially form mixed aggregates but eventually sort themselves, adhering only to cells of the same type, which would then differentiate into structures typical of their original organ.
What role do cell adhesion proteins play in cellular interactions?
There are four major families of integral membrane proteins responsible for cell-cell adhesion: selectins, members of the immunoglobulin superfamily (IgSF), integrins, and cadherins. These proteins mediate cell recognition and adhesion and help cells interact selectively with other cells.
What are the two major functions of adhesion proteins?
Adhesion proteins have two major roles: (1) providing structural support for adhesion between cells and (2) transferring information across the plasma membrane through transmembrane signaling, which influences cellular processes like growth, migration, differentiation, and survival.
How do adhesion proteins transmit signals within the cell?
Proteins like integrins and cadherins transmit signals from the extracellular environment to the cytoplasm by linking with the cytoskeleton and regulatory molecules, such as protein kinases and G proteins. These signals can alter gene expression and affect cell behavior.
What is lymphocyte homing, and how was it studied in the 1960s?
Lymphocyte homing is the phenomenon where lymphocytes return to their original sites after being removed from peripheral lymph nodes, radioactively labeled, and injected back into the body. This process was studied in vitro by allowing lymphocytes to adhere to frozen sections of lymphoid organs, where they selectively adhered to the endothelial lining of venules in peripheral lymph nodes.
What are selectins, and how do they function in cell adhesion?
Selectins are a family of integral membrane glycoproteins that recognize and bind to specific sugar arrangements in oligosaccharides on other cells. There are three known selectins: E-selectin (on endothelial cells), P-selectin (on platelets and endothelial cells), and L-selectin (on leukocytes). They mediate transient interactions between circulating leukocytes and vessel walls at sites of inflammation and clotting, with calcium required for binding.
What role do selectins play in inflammation?
During inflammation, selectins help capture leukocytes, which are flowing quickly through the bloodstream. They mediate the slowing down and rolling of neutrophils along the vessel wall, allowing for the leukocytes to stop at sites of infection or injury.
What is the process of leukocyte adhesion during acute inflammation?
In acute inflammation, venules’ endothelial cells become adhesive to neutrophils in response to chemical signals. Selectins on the endothelial cells cause the neutrophils to roll slowly along the vessel wall. Integrins on neutrophils are then activated, leading to a strong adhesion to the vessel wall.
How can selectins be blocked to reduce inflammation?
Anti-selectin antibodies can block the binding of neutrophils to selectins, preventing neutrophil rolling and reducing inflammation. Synthetic carbohydrates like efomycines can also compete with the ligands on neutrophils, preventing them from interacting with E- and P-selectins.
How do integrins contribute to the inflammatory response?
Integrins on neutrophils are activated by platelet-activating factor (PAF) on endothelial cells, which enhances their binding affinity to IgSF molecules like ICAM-1 and VCAM-1 on endothelial cells. This causes the neutrophils to stop rolling and firmly adhere to the vessel wall, facilitating their movement into the tissue.
What is leukocyte adhesion deficiency (LAD), and how does it affect the inflammatory response?
Leukocyte adhesion deficiency (LAD) is a rare disease where patients lack the ?2 subunit of integrins, which is necessary for leukocytes to adhere to endothelial cells in venules. Without this adhesion, leukocytes cannot exit the bloodstream to fight infection, leading to life-threatening bacterial infections.
What is cancer?
Cancer is a disease in which cells escape the body’s normal growth control mechanisms and proliferate uncontrollably.
How can some cancers be treated easily?
Cancers like certain skin or thyroid cancers can be cured by surgically removing the tumor if the malignant cells remain in a single mass.
Why is cancer such a devastating disease?
Cancer is devastating because malignant cells can leave the primary tumor and spread to other parts of the body through the bloodstream or lymphatic system, forming secondary tumors (metastasis).
What are metastatic cells?
Metastatic cells are cancer cells that spread from the primary tumor and initiate secondary tumors in other parts of the body.
What properties do metastatic cells have?
Metastatic cells are: 1. Less adhesive than other tumor cells, allowing them to break free from the tumor. 2. Able to penetrate barriers like extracellular matrices and basement membranes. 3. Able to survive in and colonize normal tissues.
How can metastatic cells be studied?
Metastatic cells in the bloodstream can be captured in blood samples, allowing researchers to study the tumor’s molecular characteristics, predict aggressiveness, and monitor therapy effectiveness.
Why do only a small fraction of cancer cells that enter the bloodstream form secondary tumors?
Only a small number of cancer cells can successfully invade normal tissues and survive to form secondary tumors, making metastasis a rare and complex process.
How do cancer cells penetrate extracellular matrices?
Cancer cells use matrix metalloproteinases (MMPs) to degrade extracellular matrices, allowing them to migrate through tissues and invade new areas.
What is the role of MMPs in cancer?
MMPs break down the extracellular matrix, facilitating the migration and invasion of cancer cells.
How does the extracellular matrix (ECM) change in cancer?
In cancers like breast cancer, the ECM becomes stiffer and more organized (e.g., increased collagen crosslinking), which promotes cancer cell migration.
What is the role of cell-adhesion molecules in metastasis?
The expression of cell-adhesion molecules, especially E-cadherin, influences metastasis. Loss of E-cadherin reduces cell adhesion, making cancer cells more motile and promoting metastasis.
How does E-cadherin influence cancer spread?
E-cadherin helps cells stick together, and its loss allows cells to become more mobile and invasive. Lower levels of E-cadherin correlate with higher metastatic potential in tumors.
What happens if E-cadherin expression is increased in cancer cells?
Increasing E-cadherin expression reduces a cancer cell’s ability to form tumors, as it enhances cell adhesion and suppresses metastasis.
What was discovered in a study of a family with a high rate of stomach cancer?
The study found that family members who developed stomach cancer had mutations in the E-cadherin gene, linking these mutations to increased cancer susceptibility.
What are immunoglobulins (Ig)?
Immunoglobulins (Ig), also known as antibodies, are proteins composed of polypeptide chains that contain similar domains. These domains are made of 70 to 110 amino acids and are tightly folded into specific structures.
What is the immunoglobulin superfamily (IgSF)?
The immunoglobulin superfamily (IgSF) is a group of proteins that share the Ig domain structure. It includes proteins involved in immune functions and some that mediate calcium-independent cell-cell adhesion.
How many distinct Ig domains are in the human genome?
The human genome encodes 765 distinct Ig domains, making it the most abundant domain in human proteins.
What is the evolutionary origin of Ig-like proteins?
Ig-like proteins are thought to have evolved primarily as mediators of cell-cell adhesion in invertebrates, and later took on immune system roles in vertebrates.
What is the role of IgSF cell-adhesion molecules?
IgSF cell-adhesion molecules mediate specific interactions between lymphocytes and other cells necessary for immune responses (e.g., macrophages, other lymphocytes, target cells).
What are some examples of IgSF molecules involved in cell adhesion?
Examples include VCAM (vascular cell-adhesion molecule), NCAM (neural cell-adhesion molecule), and L1 (L1CAM). Some of these mediate adhesion between nonimmune cells, like those in the nervous system.
What role do NCAM and L1 play?
NCAM and L1 play important roles in nerve outgrowth, synapse formation, and other developmental processes in the nervous system.
How does L1 deficiency affect human health?
Mutations in the L1 gene can cause severe conditions like hydrocephalus (water on the brain), mental retardation, and spasticity.
What are ligands in the context of IgSF molecules?
Ligands for IgSF molecules are proteins that bind to these molecules, facilitating various cellular interactions.
How do integrins interact with IgSF proteins?
Some integrins mediate cell-cell adhesion by binding to IgSF proteins on the surfaces of other cells.
What are cadherins?
Cadherins are a large family of glycoproteins that mediate calcium-dependent cell-cell adhesion and transmit signals from the extracellular matrix (ECM) to the cytoplasm.
How do cadherins mediate cell adhesion?
Cadherins typically join cells of similar type by binding to the same cadherin on the surface of a neighboring cell.
Why are cadherins important in tissue formation?
Cadherins are crucial for ‘sorting out’ like cells from mixed aggregates, and they play a key role in forming cohesive tissues during embryonic development and maintaining tissue structure in adults.
What are the main types of cadherins and their roles?
The main types of cadherins include E-cadherin (epithelial), N-cadherin (neural), and P-cadherin (placental).
What is the role of catenins in cadherin function?
Catenins are cytosolic proteins that associate with the cytoplasmic domain of cadherins. They tether cadherins to the cytoskeleton and transmit signals to the cytoplasm and nucleus.
How does calcium affect cadherin function?
Calcium ions form bridges between domains of a cadherin, maintaining its rigid extracellular conformation, which is essential for cell adhesion.
What happens when cadherins interact between cells?
Adhesion occurs when the extracellular domains of cadherins from opposing cells interact, forming a ‘cell-adhesion zipper.’
What is morphogenesis, and how do cadherins contribute to it?
Morphogenesis is the process of tissue and organ formation during embryonic development. Cadherins mediate dynamic changes in cell adhesion, helping cells change shape, motility, and adhesion during this process.
What is the epithelial-mesenchymal transition (EMT)?
The EMT involves cells changing from a tightly adherent epithelial layer to solitary, nonadhesive, and migratory mesenchymal cells.
How does cadherin expression change during neural development?
In the formation of the nervous system, cells stop expressing E-cadherin and begin expressing N-cadherin, leading to the separation of epithelial cells and the formation of the neural tube.
How many cadherins have been identified in humans?
Over 100 cadherins have been identified in humans, many of which are thought to be functionally redundant.
What genetic diseases are linked to cadherin mutations?
One notable genetic disease linked to cadherin mutations is Usher syndrome, which causes deafness and gradual vision loss.
What is the role of cadherin 23 and protocadherin 15 in the inner ear?
Cadherin 23 and protocadherin 15 form ‘tip links’ between stereocilia in hair cells of the inner ear.
What happens when there are mutations in tip links?
Mutations in tip links can result in defects in stereocilia organization, leading to profound deafness.
What are adherens junctions and where are they found?
Adherens junctions are specialized intercellular junctions primarily found in epithelial tissues. They are especially common in the lining of the intestine.
How do adherens junctions mediate adhesion between cells?
Adherens junctions mediate cell adhesion through calcium-dependent linkages formed between the extracellular domains of cadherins.
What is the function of adherens junctions in cells?
Adherens junctions have two main functions: Mechanical adhesion and signal transmission.
What are desmosomes, and where are they found?
Desmosomes are specialized structures that provide strong adhesion between adjacent cells, primarily found in tissues that experience significant mechanical stress.
What is the function of adherens junctions in cells?
Adherens junctions have two main functions: Mechanical adhesion connects the exterior environment to the actin cytoskeleton. Signal transmission provides a pathway for signals to be transmitted from the cell exterior to the cytoplasm, such as survival signals in endothelial cells.
Mice lacking endothelial cell cadherins cannot transmit these survival signals, resulting in embryonic death.
What are desmosomes, and where are they found?
Desmosomes are disk-shaped adhesive junctions about 1 µm in diameter. They are found in tissues that are subject to mechanical stress, such as cardiac muscle, skin, and the uterine cervix.
How do desmosomes differ from adherens junctions in terms of cadherins?
Desmosomes use a different set of cadherins compared to those in adherens junctions. The cadherins in desmosomes are called desmogleins and desmocollins, while the classical cadherins in adherens junctions are typically E-cadherin, N-cadherin, and others.
How do desmosomes provide structural integrity to tissues?
Desmosomes anchor intermediate filaments (such as keratin) to the cytoplasmic domains of desmosomal cadherins via dense cytoplasmic plaques. This network of intermediate filaments provides structural continuity and tensile strength, enabling tissues to withstand mechanical stress.
What is the role of desmosomes in pemphigus vulgaris?
In pemphigus vulgaris, an autoimmune disease, antibodies target desmogleins (cadherins in desmosomes), causing a loss of epidermal cell-cell adhesion. This leads to severe blistering of the skin due to weakened cell cohesion.
What are tight junctions and where are they found?
Tight junctions (TJs) are specialized connections between neighboring epithelial cells, typically located at the most apical end of the junctional complex. They are found in various epithelial tissues, including the lining of the intestine, lungs, and the walls of the urinary bladder.
What is the main function of tight junctions?
Tight junctions serve as barriers to prevent the free diffusion of water and solutes between cells in an epithelial sheet, thus maintaining the integrity of the tissue. They also help maintain the polarized nature of epithelial cells by preventing the movement of membrane proteins between the apical and basal surfaces of the cell.
How do tight junctions form their seal?
The membranes of neighboring cells in tight junctions make contact at intermittent points, forming a series of connected strands. These strands consist of aligned integral membrane proteins that encircle the cell like a gasket, creating a seal to block solute diffusion across the epithelium.
What proteins are involved in tight junctions?
Tight junctions primarily consist of the proteins occludin and claudins. Claudins form the main structural components of tight junctions, and at least 24 different types of claudins have been identified.
How do tight junctions affect permeability?
Tight junctions can exhibit varying permeability depending on their structure and the specific claudins involved. Some TJs are selectively permeable to specific ions or solutes, such as magnesium ions (Mg2+) in the kidney tubules, while others can form more impermeable seals.
What is the significance of claudin-16 in kidney function?
Claudin-16 is expressed in the thick ascending limb of kidney tubules and plays a role in selectively allowing magnesium ions (Mg2+) to pass through tight junctions. Mutations in the claudin-16 gene can lead to a rare disease with abnormally low magnesium levels in the blood.
How do tight junctions contribute to skin impermeability?
Tight junctions in the outer layers of the epidermis are crucial for preventing water loss. Mice lacking claudin-1, a key protein in these junctions, experience uncontrolled water loss and dehydration.
What role do tight junctions play in the blood-brain barrier?
Tight junctions between endothelial cells in the blood-brain barrier prevent unwanted substances from passing from the bloodstream into the brain, thus protecting the brain from harmful solutes.
How do tight junctions affect drug delivery to the brain?
The blood-brain barrier, formed by tight junctions, can block the passage of therapeutic drugs into the central nervous system. This presents a challenge for drug delivery.
