MICROTUBULE CONSTRUCTION a. Dimerization of a and b tubulin subtypes b. Linear repitition of the heterodimers makes a MOUVEMENT -Centriole a b - a b - a b - a b - a b - a b - a b - a b - a b - a b + Microtubule organizing tubulin protofilament growing -Centrosome center -Kinetochore c. Side-by-side assembly of 13 protofilaments to make a sheet -Axonène d. Rolling of the sheet into a tubule -Cellule ciliée + e. Elongation controlled by [ions] [a b ] GTP GDP rate Colchicine blocks elongation BUILD A CENTRIOLE or BASAL BODY Assemble 2 partial & one CENTRIOLES - MTOC - complete microtubules into KINETOCHORES a TRIPLET C 10 B subfibers 10 13 A protofilaments Arrange 9 triplets in parallel & position an identical array nearby & perpendicular CENTROSOME = 2 Centrioles + Microtubule Organizing Center 1 • The cell cycle and mitosis: mechanism (example) nonkinetochore kinetochore microtubule microtubules MICROTUBULES BUILD AN AXONEME of cilium or flagellum The axoneme has a 9 double MT + 2 center MT pattern with dynein arms on the outside for sliding action! Extend A & B subfibers to be the axoneme’s doublets This is the “Sliding Filament Theory” B 10 subfibers 13 protofilaments A 9 doublets central pair Other microtubule arrays are the MITOTIC SPINDLE & AXONAL CORE 2 MICROTUBULES FOR THE CILIARY BEAT Dynein arm with ATPase activity to power movement - generating a sliding interaction with B subfiber of adjacent microtubule doublet Connections turn the microtubule sliding into BENDING of the Cilium 3 MICROTUBULES FOR THE CILIARY BEAT CILIATED AIRWAY CELL Dynein arm with ATPase 9 + 2 Microtubular array (9 doublets) activity to power movement - CILIUM generating a sliding interaction Basal bodies with 9 + 0 array (9 triplets) with B subfiber of adjacent . Zonula occludens microtubule doublet . Zonula adherens Macula adherens/Desmosome Connections turn the microtubule GOLGI Keratin Intermediate Filaments sliding into BENDING of the Cilium Centrioles & MTOC MEDICAL CORRELATIONS for Microtubules A genetic axonemal dynein deficiency impairs ciliary clearance of luminal the airway, leading to severe lung infections of Kartegener’s Actin cortex syndrome lateral Hemi-desmosome Dangerous cell proliferation in cancer can be halted by vinblastine . which blocks mitotic spindle formation BL basal SENSORY STEREOCILIA ON AUDITORY HAIR CELL SENSORY STEREOCILIA ON AUDITORY HAIR CELL bundled, as the as the core of the stereocilium Stereocilia are core of the stereocilium non-motile, Actin filaments Ion channels Actin filaments opened by but can be deflection of meshwork, as anchoring moved by the meshwork stereocilium cuticular plate stimulus Stereocilia are non-motile, Hair cell also but can be has a solitary moved by the tall true stimulus cilium, with microtubules Synapses 4 SENSORY STEREOCILIA ON AUDITORY HAIR CELL bundled, as the as the core of the stereocilium Actin filaments meshwork Note: no Ion channels microtubules in the signal-transduction mechanism & Stereocilia are non-motile So why the ‘cilium’ name? Why, indeed! Synapses Dynein arms move across adjacent MTs and cause sliding and axonemal bendingmotion 5 CELL SHAPES VARIETIES OF MOVEMENT 1 Cylindrical/columnar, cuboidal, polyhedral, flattened Ciliary & Flagellar Whole cell epithelial cell shapes to fit into multicellular patterns Intracellular vesicles Extension of processes 2 Spheroid & Ovoid - defensive blood cells Chromatids during mitosis Separation of cells at mitosis 3 Elongated - muscle cells & fibroblasts Whole cell (sperm) Intracellular vesicles 4 Multiple branching processes - neurons, glial cells, pigment cells by MICROTUBULES by ACTIN FILAMENTS Generalizations Generalization Little direct motor role for Intermediate Filaments Microtubules and intermediate filaments with cell junctions Microtubules & IFs highly concentrated around the nucleus & hold shape and polarization extend radially; actin more peripheral under the plasmalemma in the “cortex” Exceptions are: muscle, neurons, mature epidermal cells, RBCs Actin microfilaments (with & without myosin) modify shape Movements are closely related to cell’s shape & polarity 6.