Tissue Architecture Flashcards
Tissue Level Function
-muscle movement
Cellular Level Functions
– Cell morphology/shape
– Motility
– Cell adhesion
– Division
Subcellular Level Functions
– Organization – Tensile strength – Chromosome segregation – Cell polarity – Vesicular movement
Cytoskeletal filaments are ___ and ___.
dynamic and adaptable
Cytoskeletal filaments
- intermediate filaments
- microtubules
- microfilaments
Intermediate Filaments
• Great tensile strength
– Enable cells to withstand mechanical stresses
• Found in cytoplasm of most animal cells
– Form a network throughout cytoplasm
– Surround the nucleus and extend to periphery
• Often anchored to plasma membrane at cell- cell junctions
• Form mesh-like structure called nuclear lamina
– Underlies and strengthens nuclear envelope
• Rope-like properties give high tensile strength
• Often further stabilized by accessory proteins
– Cross-link filaments into bundles
– Link to microtubules, actin filaments, and cell-junctions
Microtubules
• Crucial organization role in all eukaryotic cells
• Long and stiff hollow tubes
• Rapid assembly and disassembly
• Extend from centrosome to cell periphery
– Create “tracks” to transport vesicles, organelles and other cell components
• Form mitotic spindle for chromosome segregation
• Part of cilia and flagella
Microfilaments
• Actin filaments (F-actin) – Twisted polymer of G-actin (globular) – Structural polarity • Present in all cell types • Many are unstable – Association with other proteins can form stable structures • Essential for cell movements – Locomotion, phagocytosis, cell division, contraction, etc • Many proteins bind to and modify actin properties – Stabilize – Strengthen – Cross-link – Organize
ECM and Basal Lamina
• Components produced intracellularly and secreted and aggregate
– Composed of interlocking fibrous proteins and proteoglycans
• Matrix which interacts with cells/tissues via transmembrane proteins
– Anchors/clusters cells into tissues with distinct function
• Composition and properties controlled and vary by tissue type, location etc.
– Strength in tendons, strength and rigidity in teeth and bones, cushioning in cartilage
Collagen
• Main structural protein in ECM/connective tissue and basal laminae
– 28 distinct types of collagen
• Trimeric proteins – Homotrimers
– Heterotrimers
– Form collagenous triple helix
• Associate as fibers, sheets or transmembrane structures
• Nutrient deficiencies and genetic conditions in clinical conditions
Ehlers-Danlos Syndrome
• Caused by a mutation in collagen or collagen synthesis genes
– Fibrous Proteins: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB
– Enzymes: ADAMTS2, PLOD1, B4GALT7, DSE, and D4ST1/CHST14
• Mutations alter the structure, production, or processing of collagen or proteins that interact with collagen
• Weakens connective tissue in the skin, bones, blood vessels, and organs
Cell Connections and Junctions
• Cell junctions link cells to neighboring cells,
• Focal contacts link cells to extracellular matrix, or basil lamina
• Roles in migration, immune system function, wound healing, tissue architecture
• Also involved in intracellular signaling pathways
– Cell death/survival, secretion, etc…
Cell Adhesion Molecules (CAMs)
• 3 major domains
– Extracellular (binding to adjacent cell/matrix proteins
– Transmembrane (links CAM to membrane)
– Cytoplasmic (bind to cytoskeleton via linker proteins)
Catherine Superfamily
• Ca2+ dependent adhesion molecule – Important in formation of junctions between cells (epithelial “sheets”) • Desmosomes and adherens junctions – Homophilic interactions (extracelluar) – Interacts with cytoskeleton (actin) • E-cadherin – Epithelial cadherin • N-cadherin – Neural cadherin • VE-cadherin – Vascular-endothelial cadherin • LI-cadherin – Liver-intestine cadherin
EMT and Cadherin Switching
• Cadherins can serve as biomarkers for invasive, metastatic tumors
• EMT
– Epithelia to Mesenchymal Transition
Less invasive
– In transitional bladder cancer
– in E-cadherin and in N- cadherin
– Increased invasiveness of the tumor cells
– Increased metastatic potentialIg Superfamily CAMs
– Family of more than 25 Calcium-independent
transmembrane glycoproteins
• Immune cell interactions
• ICAM, VCAM-1, PECAM-1, NCAM
– Contain a variable number of immunoglobulin-like domains
– Expressed on vascular endothelial cells and bind to various integrin molecules
• MAdCAM-1
– Contain Ig-like and mucin-like domains
– Expressed on mucosal endothelium to direct lymphocyte entry into mucosa
– Homophilic and heterophilc binding
– Involved in recognition, binding, or adhesion processes of cells
Selectins
– Family of calcium dependent glycoproteins
– Bind to extracellular carbohydrates
– Play important roles in host defense mechanism
• Increased presentation during local inflammatory response
• WBC surface makers include carbohydrates which act as ligands for selectins
• Low-affinity of selectins to ligands allows for leukocyte “rolling” during leukocyte adhesion cascade
– Include:
• Endothelial (E)-selectin
• Leukocyte (L)-selectin
• Platelet (P)-selectin
Integrins
• 15 α and 8β subunits form over 20 heterodimeric integrins
• Couple the extracellular matrix to cell cytoskeleton
– Fibronectin, collagen, laminin, vitronectin
– Aid cell in endure pulling forces
• Can activate signaling pathways
– Interactions with receptor tyrosine kinase
– Take part in regulating growth, division, survival, differentiation, apoptosis
• Cell-Cell interactions via β2 family
– Integrins on leukocytes allow for adhesion and transmigration to sites of infection
Taxol
Binds and stabilizes microtubules
-prevents rapid growth and is used to treat cancer
Colchicine, colcemid
Binds tubulin diners and prevents their polymerization
Vinblastine, vincristine
Binds tubulin diners and prevents polymerization
Phalloidin
Binds and stabilizes filaments (actin)
Cytochalasin
Caps filament plus ends, preventing polymerization there
-microfilaments
Latrunculin
Binds actin monomers, and prevents their polymerization
Scurvy
- loss of cofactor (ascorbate or iron)
- wounds re open
Collagen-RER
Synthesis if procollagen
Collagen lumen of ER
Hydroxylation of proline and lysine residues; glycosylation of selected hydroxylysine residues
Collagen- lumen of ER and golgi
Self assembly of the tropocollagen molecule, initiated by disulfide bond formation in the carboxy-terminal extensions; triple helix formation
Collagen- Secretory vesicle
Procollagen prepared for secretion from cell
Collagen- extracellular
Cleavage of the propeptides, removing amino and carboxy terminal extensions, self assembly of the collagen molecules into fibrils and then fibers
