Cell Polarity And Cell Crawling PDF

Cell Polarity ============= cell polarity: asymmetric organization of plasma membrane, cytoskeleton, organelles Mechanism of Cell Crawling ========================== protrusion: actin-polymerization-dependent with the attachment of a lamellipodium at the leading edge (green arrows at the fron...

Cell Polarity ============= cell polarity: asymmetric organization of plasma membrane, cytoskeleton, organelles Mechanism of Cell Crawling ========================== protrusion: actin-polymerization-dependent with the attachment of a lamellipodium at the leading edge (green arrows at the front)\ contraction: at the rear of the cell, it propels the body of the cell forward (green arrow at the back)\ traction: new focal contacts are made at the front, and old ones are disassembled at the back as the cell crawls forward Lamellipodia ============ lamellipodia: a two-dimensional network of actin filaments, at the leading edge of moving cells\ lamellum (plural, lamellae): it is behind the lamellipodium; its actin network is more stable than that of lamellipodia\ polymerization of actin filaments at the leading edge leads to membrane protrusion that facilitates the binding of cell surface receptors to the ECM; new adhesions form\ contractions produced by stress fibers generate tension that pulls the cell forward; at the same time, focal adhesion disassembly retracts the trailing cell edge Filopodia ========= one-dimensional, with parallel bundles of actin filaments; the filaments have their barbed end towards the protruding membrane\ sensors of the extracellular environment (through cell surface receptors)\ embedded in, or protruding from, a lamellipodium\ assembly: nucleation, sustained barbed end elongation, and filament bundling\ role in cell migration, neurite outgrowth, and wound healing External Signals Guiding Cell Migration ======================================= signals: chemical and physical\ chemotaxis: cell movement in a direction of a diffusible chemical\ neutrophils move to bacterial infection by detecting N-formylated peptides from bacterial proteins; ligand-receptor binding stimulates actin polymerization\ some signals are immobilized on the ECM or cells\ most long-distance cell migrations depend on diffusible and non-diffusible signals\ persistent migration is achieved through microtubules Cilia and Flagella ================== cellular appendages from microtubules and dynein\ cilia have a whip-like motion; propel cells through fluids or move fluids over the cell surface\ flagella on sperm enable swimming\ basal bodies root cilia and flagella at the cell surface; the basal bodies are derived from centrioles embedded in the cell surface\ have a core (axoneme): nine doublet microtubules in a ring around a pair of single microtubules; dynein forms bridges between doublet microtubules Cilia and Flagella ================== movement is due to the bending of the core (axoneme)\ dyneins attempt to walk along the adjacent microtubule doublet, forcing adjacent doublets to slide relative to one another; however, the other links between the microtubule doublets prevent sliding, and the dynein force is converted into bending Neuronal Specialization Depends on the Cytoskeleton =================================================== neurons have processes to receive (dendrites) or transmit electrical signals (axons); in axons, microtubules are oriented with their minus end to the center of the cell body\ mitochondria, proteins in vesicles, and synaptic vesicle precursors are carried by the plus end-directed kinesins on microtubules\ old components from the axon terminals are carried back for degradation to the cell body, on microtubules by dyneins\ actin filaments line the cortex of the axon; motor proteins such as myosin V are abundant\ microtubules behind the growth cone are constantly growing/shrinking (dynamic instability) Platelet Activation =================== platelet activation is a sequence of actin filament severing, uncapping, elongation, recapping, and crosslinking\ gelsolin is a Ca2+- and phosphoinositide 4,5-bisphosphate (PIP2)-regulated actin filament severing and capping protein Putting It Together =================== polarity dictates the function and fate of cells\ cell crawling requires structural polarity, which is influenced by external cues\ "crawling" coordinates protrusion at the leading edge (by the assembly of actin filaments), adhesion of the protruded cell part to the substratum, traction via molecular motors to bring the cell body forward, and disassembly of old cell-substratum contacts\ in neurons, dendrites and axons require the coordinated assembly of microtubules, neurofilaments, actin filaments, and molecular motors that transport subcellular components\ platelet activation requires the coordination of actin filament severing, uncapping, elongation, recapping, and crosslinking