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Cell bio 2 wks ago
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Multiadhesive Glycoproteins
Proteins in the ECM that promote cell adhesion.
Ground Substance
A component of the ECM containing primarily glycosaminoglycans (GAGs), proteoglycans, and glycoproteins.
Extracellular Matrix (ECM)
The organized meshwork of macromolecules surrounding and underlying cells.
Fibers
Structural components of the ECM that vary in composition.
Composition of ECM
Varies in composition, containing ground substance, multiadhesive glycoproteins, and fibers.
Extracellular Environment
Includes the ECM, water, and other small molecules, constituting the environment outside the cells.
Metabolic Activities
The activities of cells that can be affected by the ECM.
Cell-ECM Interactions
The influence of the ECM on the shape, migration, and interactions of cells.
Cell Differentiation
The process influenced by the ECM, leading to cells taking on specialized functions.
Physical Support
Provided by the ECM against compressive and tensile forces.
ECM Function
Affects cell metabolism, shape, migration, interactions, division, and differentiation, while also providing physical support.
What is the watery largely unstained extracellular material rich in hydrated glycosaminoglycans?
Ground substance (the extracellular matrix, ECM)
What are Glycosaminoglycans (GAGs)?
They are a family of unbranched polysaccharide chains of repeating disaccharide units with multiple negative charges that constitute a large volume fraction of the ECM.
What is the structure of Glycosaminoglycans (GAGs)?
They are a polymer of repeating disaccharide units.
What is the function of Glycosaminoglycans (GAGs)?
They bind H2O in connective tissue due to their negative charges and act as a cushion, allowing tissue to temporarily adapt its shape under externally applied stress and then return to its original state.
Proteoglycans
Proteins with numerous covalently linked GAG side chains
Proteoglycans Function
Bind H2O, shock absorption, supportive function (e.g., in cartilage), resistance to compression of articular cartilage, formation of cell-cell junction or cell-matrix junction, signaling and regulatory functions (e.g., by binding signaling molecules)
Ground Substance
The extracellular matrix (ECM)
Glycoproteins
Proteins with short carbohydrate side chains that contribute to the organization of the extracellular matrix by offering specific binding sites for cells and other matrix molecules
Glycoproteins Examples
Fibronectin, Laminin
Fibronectin
Glycoprotein important for cell-matrix interactions, binds to collagen and integrins, plays an important role in embryogenesis, regulates cell migration and hemostasis, crosslinking of fibrin molecules with thrombocytes and fibroblasts
Laminin
Major component and organizer of the basal lamina besides type IV collagen, binds to collagens, integrins, and proteoglycans
What is the repeating amino acid sequence in a collagen molecule?
GlyXYn
What is the first amino acid of the GlyXYn triplet in the collagen molecule?
Glycine
What is the most common amino acid in position X of the GlyXYn triplet in the collagen molecule?
Proline
What is commonly found in position Y of the GlyXYn triplet in the collagen molecule?
Hydroxyproline or hydroxylysine
What is the function of collagen in the body?
To organize, strengthen, and provide elasticity to the extracellular matrix
How many types of collagen triple helices can be assembled from the 42 genes coding for collagen chains?
28 types
Where does the modification of the polypeptide chain of collagens occur during collagen synthesis?
Rough endoplasmic reticulum (ER)
These very large molecules are enclosed in vesicles, transported to the cell membrane via the Golgi apparatus, and secreted via exocytosis in the extracellular space.
Collagen synthesis.
The propeptides at the end of the collagen propeptide chains are split off.
Collagen 6.
The formed tropocollagens are crosslinked to fibrils.
Fibrillogenesis.
In the extracellular space, several of these fibrils form collagen fibers.
Collagen synthesis.
Vitamin C deficiency clinical manifestation
Scurvy
Symptoms of vitamin C deficiency
Swollen gums, poor wound healing, mucosal bleeding, curly body hair, follicular hyperkeratosis, generalized weakness/fatigue
Type I collagen
90% of body collagen, found in bone, produced by osteoblasts, skin, tendons, ligaments, fascia, dentin, cornea, internal organs, scar tissue, late stages of wound healing.
Osteogenesis imperfecta
Type I collagen decreased production due to various genetic defects, most commonly autosomal dominant mutations in COL1A1 or COL1A2 genes, leading to impaired synthesis of normal type I collagen and bone matrix formation. It affects osteogenesis in the body, leading to brittle bones and osteoporosis.
Growth delay
Delayed or stunted growth in children, a common symptom of osteogenesis imperfecta.
Skeletal deformities
Abnormalities in the bone structure, such as curvature or malformation, often seen in osteogenesis imperfecta.
Brittle bones
Fragile, easily broken bones, a characteristic feature of osteogenesis imperfecta.
Bowing of bones and saber shins
Curvature or bowing of the long bones, particularly the legs, and the development of saber-shaped shins, associated with osteogenesis imperfecta.
Fractures during childbirth and recurrently from minimal trauma thereafter
Fractures that occur during the birthing process in infants with osteogenesis imperfecta, and continued susceptibility to fractures from minor impacts throughout life.
Blue sclerae
A bluish tint in the whites of the eyes, caused by the visibility of underlying choroidal veins due to thin and translucent sclera, commonly seen in osteogenesis imperfecta.
Progressive hearing loss
Gradual loss of hearing over time, often associated with osteogenesis imperfecta.
Type II collagen
A type of collagen found in cartilage, including hyaline cartilage, vitreous humor of the eye, intervertebral discs, and nucleus pulposus, commonly affected in osteogenesis imperfecta.
Type III collagen
A type of collagen found in reticular fibers in skin, blood vessels, granulation tissue, uterus scar tissue, early stages of wound healing, fetal tissue in early embryos, and throughout embryogenesis, associated with osteogenesis imperfecta.
Type IV collagen
A type of collagen found in basement membranes and the lens, affected in osteogenesis imperfecta.
Type V collagen
A type of collagen found in bone, skin, fetal tissue, and placenta, implicated in osteogenesis imperfecta.
Defect: Ehlers-Danlos syndrome classic type
Inherited connective tissue disorder that affects the collagen, leading to skin hyperextensibility, joint hypermobility, and tissue fragility.
Collagen
A fibrous protein that provides strength and elasticity to connective tissues, such as bones, cartilage, tendons, and skin.
Ehlers-Danlos syndrome
A genetic disorder caused by mutations in the genes controlling the synthesis of collagen. It is characterized by hyperextensible skin, joint hypermobility, and a tendency to bleed.
Collagen
An elastic protein that is a major component of elastic fibers. It is rich in the nonhydroxylated amino acids glycine, proline, and lysine, and provides tissue with elasticity.
Elastin
A protein found in tissues requiring high elasticity and the ability to recoil after a transient stretch. It is found in large arteries (e.g., aorta), lungs, skin, vocal folds, and elastic ligaments.
What are the types of cell junctions?
Cell-cell junctions and cell-matrix junctions
What are the three functional classes of cell junctions?
Occluding junctions, anchoring junctions, and communicating junctions
Tight junction
Zonula occludens sealing contact that forms an intercellular barrier between epithelial cells
Membrane proteins claudins and occludins
Interact between two cells in a tight junction
Connected to actin filaments of the cytoskeleton
Via adapter proteins usually at the apical surface between epithelial cells
Function
Seals adjacent epithelial cells together and separates the apical from the basal side of the epithelium, prevents paracellular transport, and serves as a diffusion barrier
Anchoring junctions
Mechanical attachments between cells
Several forms of anchoring junctions
Desmosomes, hemidesmosomes, adherens junctions
Structure of adherens junction
Vinculin and catenin on the intracellular side, connecting actin filaments with transmembrane adhesion proteins such as cadherins
Function of adherens junction
Connects epithelial cells and endothelial cells in a continuous belt-like manner
Role of cadherins
Calcium-dependent transmembrane proteins responsible for adhesion of cells to other cells. Mainly E-cadherin
Loss of cadherins
Associated with metastatic transformation in neoplasias
Adherens junction
Also known as zonula adherens or belt desmosome. It tightly connects cells across a broader belt-shaped area
What are adherent junctions formed by?
Adherent junctions are formed by interacting proteins of the cadherin family, creating strong points of attachment that hold together cells of the epithelium.
What structure may adherent junctions form?
Adherent junctions may form zonula adherens that encircle epithelial cells just below their tight junctions.
What are the other names for adherent junctions?
Adherent junctions are also known as anchoring junctions or adhering junctions.
What are desmosomes?
Desmosomes are cell junctions that adhere cells together through the linking of two cells via intermediate filaments. They contain cadherins, mainly desmoglein and desmocollin.
What is pemphigus vulgaris?
Pemphigus vulgaris is a disease characterized by autoantibodies against desmoglein 1 and/or 3, leading to the disruption of desmosomes.
Autoimmune blistering skin disorder
Pemphigus Vulgaris
Peak incidence
40-60 years of age
Location of recurrent lesions
Scalp, face, trunk, regions of pressure
Hemidesmosome function
Connects epithelial cells with the basal lamina and maintains the integrity of the basement membrane
Cell Junction
Bullous pemphigoid autoantibodies against hemidesmosomes
Cell Junction
Anchoring junctions adhering junctions
Autoimmune blistering skin disorder caused by circulating antibodies against hemidesmosomes
Bullous Pemphigoid
Tense subepidermal blisters develop and can become hemorrhagic
Bullous Pemphigoid
Peak incidence in people above 60 years of age
Bullous Pemphigoid
Recurrent lesions typically occur in skin flexures eg groin, axilla, and over the abdomen
Bullous Pemphigoid
Mucous membranes are usually spared
Bullous Pemphigoid
Cell Junction: Communicating junctions that permit the passage of electrical or chemical signals
Gap junction
Intercellular channels that connect two cells formed by the interaction of the connexons of two neighboring cells
Gap junction
Communicating junctions that control the passage of electrical stimulus in cardiomyocytes
Gap junction
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A flashcard deck covering cell biology topics from 2 weeks ago, including ECM, collagen, and cell junctions.
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