Lecture 14 - Cytoskeleton_ tubulin.pdf

Cytoskeleton: Microtubules 1 BIOL2020 Prof. Nicanor González actin and microtubules T. Wittmann The cytoskeleton maintains cell shape, organization, and provides support for internal and external movement. actin and microtubules The cytoskeleton maintains cell shape, organization, and provides...

Cytoskeleton: Microtubules 1 BIOL2020 Prof. Nicanor González actin and microtubules T. Wittmann The cytoskeleton maintains cell shape, organization, and provides support for internal and external movement. actin and microtubules The cytoskeleton maintains cell shape, organization, and provides support for internal and external movement. C.Leterrier ● ● They are cytoplasmic proteins Non-overlapping functions actin N.Efimova actin and microtubules T. Wittmann The three classes of cytoskeletal filaments are microfilaments, microtubules, and intermediate filaments Microfilaments Actin Microtubules Tubulin Intermediate Filaments Various proteins Desmin, Lamin, Keratin, etc Structure and assembly of microtubules Microtubules are polymers of the protein tubulin. The tubulin subunit is a heterodimer formed from two closely related globular proteins called ɑ-tubulin and β-tubulin ● ● Microtubules have polarity They are hollow tubes A microtubule is built from 13 parallel protofilaments, each composed of αβ-tubulin heterodimers stacked head to tail and then folded into a tube The helical microtubule lattice make them stiff and hard to bend The helix forms from a slight stagger in the protofilament lateral contacts the orientation of their subunits gives microtubules polarity: the microtubule plus end grows and shrinks much more rapidly than its minus end. Rapid microtubule growth occurs by the addition of tubulin dimers at the ends ● ● ● Lag phase Elongation phase Plateau phase Microtubule nucleation is the process in which several tubulin molecules interact to form a microtubule seed Microtubule nucleation is the process in which several tubulin molecules interact to form a microtubule seed. ● ● ● Tubulin dimers assemble into protofilaments laterally associated linear protofilaments Nucleation is slow Microtubules Undergo a Process Called Dynamic Instability, in which individual microtubules alternate between cycles of growth and shrinkage The addition of GTP-tubulin to plus end of a protofilament causes the end to grow in a linear conformation that assembles into the cylindrical wall of the microtubule. Stable→ Not stable→ Tracking microtubule dynamics with fluorescence microscopy https://youtu.be/nwmvYuXcgYY https://youtube.com/shorts/tzcYZP CqVkk?feature=share https://youtu.be/W_JInYcsrWU The change from growth to shrinkage is called a catastrophe, while the change from shrinkage to growth is called a rescue. Hydrolysis of GTP after assembly changes the conformation of the subunits and tends to force the protofilament into a curved shape that is less able to pack into the microtubule wall. Nucleation in many cases depends on the γ-tubulin ring complex. Microtubules are generally nucleated from the microtubule-organizing center (MTOC) where γ-tubulin is most enriched. Many animal cells possess a single, well-defined MTOC called the centrosome Centrosomes are composed of two centrioles and surrounded by a dense mass of protein termed the pericentriolar material microtubules start at the pericentriolar material γ-tubulin is in the pericentriolar material Unless the cell is dividing, γ-tubulin is in a single spot: the centromere ● https://www.cell.com/action/showPdf?pii=S0092-8674%2806%2900654-4 Microtubule associated proteins (MAPs) bind and stabilize microtubules Map2 and Tau set the spacing of the microtubule bundles Tau Mutations cause Neurodegenerative Diseases (e.g., Alzheimer's disease) actin and microtubules tau MAP2 C.Leterrier