The mechanics of cell division An overview of M

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					                                                                                   An overview of M phase
                                                                            • Nuclear division
                                                                               – Segregate and distribute
                                                                                 duplicated chromosomes
    The mechanics of cell division                                          • Cytoplasmic division
                                                                               – Cytokinesis
                                                                            • These two division
                              BIOS 662                                        processes are driven by
                              Fall 2007                                       specialized cytoskeletal
                                                                              machines
                              X. Wang




     Cohesins and Condensins                                                         Cytoskeletal machines
                                                                               • Nuclear division
                                                                                   – Bipolar mitotic spindle
• Cohesins                                                                             • Microtubules
     – Multisubunit protein                                                            • Microtubule-dependent
       complexes                                                                         motor proteins
     – Glue the two copies of                                                          • Other proteins
       each replicated
       chromosome together as
                                                                               • Cytokinesis
       sister chromatids                Gently coiled        metaphase             – In mammalian cells and
                                                                                     eukaryotes
• Condensins                                                                           • Contractile ring
     – Proteins                                                                            – Actin and myosin
     – Compact of replicated                                                                 filaments
       chromosomes                                                                 – In plants
       (chromosome                                                                     • Phragmoplast
       condensation)                                                                       – Construct a new cell
                                                                                             wall between the two
                                                                                             sets of replicated
                                        Blue: DNA; Red: condensin complex                    chromosomes




                                                                               Centriole replication and the
      Duplication of centrosome                                                     centrosome cycle
•   Centrosome is duplicated when
    DNA is duplicated in the
    interphase
•   Components of centrosome
      – A pair of centrioles
      – Matric (many proteins)
•   Function of duplicated
    centrosome
      – The principle microtubule
        organizing center
      – Initiate the formation of the
        bipolar mitotic spindles
      – Each daughter cell has its
        own centrosome




                                                                                                                    1
       The course of mitosis in a typical animal cells


• Five stages
   – Prophase
   – Prometaphase
   – Metaphase
   – Anaphase
   – Telophase



                                                                                    Plant cell mitosis (prophase, prometaphase, metaphase, anaphase, telophase)



                           Green: microtubules, blue: chromatin




                                                                                              Mitotic spindle
                                                                               • Microtubule- dependent
                                                                                 motor proteins
                                                                                  – Kinesin-related proteins:
                                                                                    move towards plus end
                                                                                    of microtubules
                                                                                  – Dynesins: move towards
                                                                                    minus end
                                                                               • Spindle microtubules
                                                                                  – Astral microtubules: all
                                                                                    directions
                                                                                  – Kinetochore
                                                                                    microtubules: centromere
                                                                                  – Overlapping
                                                                                    microtubules: interdigit at
                                                                                    the equator, responsible
                         Mitosis in an animal cell                                  for the bipolar shape of
                                                                                    the spindle




                  Microtubule instability
                                                                                Microtubule instability (cont’d)
    • Switch between growth
      and shrinkage
    • Catastrophe: the switch                                               • The balance
      form growth to                                                          between
      shrinkage
                                                                              catastrophins and
       – Regulated by proteins
         called catastrophins,                                    Normal
                                                                              MAPs influences the
         which destabilize                                                    frequency of
         microtubule arrays
    • Rescue: the switch from                                                 microtubule
      shrinkage to growth                                                     catastrophes and
       – M-Cdk activates                                          MAP         microtubule length
         microtubule motor                                        deleted
         proteins and microtubule-
         associated proteins
         (MAPs) by
         phosphorylation                   Abnormal spindle formation




                                                                                                                                                                  2
              Spindle assembly
                                                                      Motor proteins
                                                          • Plus-end directed motor
• The balance between                                       proteins push the two
  catastrophins and                                         halves of spindle apart
  MAPs creates dynamic                                    • Minus-end directed
  microtubules                           Spindle pole       motor proteins pull them
• Motor proteins move                                       together
  one microtubule relative                                • The balance between
  to the other with the                                     plus-end directed motor
  direction of movement                                     proteins and minus-end
  dependent on the                                          directed motor proteins
  polarity of motor                    Overlap zone         determine the spindle
  proteins and                                              length
  microtubules




Kinetochores attach chromosomes to the
            mitotic spindle
                                                             Kinetochore capture microtubules

• Kinetochore
   – A complex protein
     machine that
     assemble onto the
     condensed DNA at
     the centromere
     through the plus-end
     of the microtubule (a
     kinetochore
     microtubule)




                                                         Microtubules are highly dynamic in the
                                                                  metaphase spindle

                                                        • The free-plus end
                                                          shifting stochastically
                                                          between slow growth
                                                          and rapid shrinkage
                                                                                          Activated frog xenopus egg (caged fluorescein labeled microtubule
                                                        • Kinetochore and
                                                          overlap microtubules
                                                          exhibit poleward flux
                                                           – Net increase of tubulin at
                                                             the plus-ends, balance
                 Green: microtubules                         the net loss st the minus
                 Blue: DNA                                   ends
                 Red: kinetochores
                                                                                              Low amount of fluorescent tubulin is injected
                                                                                              into living cells




                                                                                                                                                             3
Functional bipolar spindles can assemble
  around chromosomes in cells without                                        Sister chromatids separation
              centrosomes
                                                                            • APC(anaphase
                                                                              promoting complex)
                                                                              activation
                                                                               – Inactivate M-Cdk                                    metaphase
                                                                               – Cleave securin (an
                                                With centrosomes
                                                                                 inhibitory protein)
                                                                               – Activate separase ( a
                                                                                 protease)
                                             Without centrosomes
                                                                               – Separase cleave the
                                                                                 cohesin complex
     No centrosomes or kinetochores
                                                                               – Unglue sister chromatids
                                                                                                                                       anaphase




   The major forces that separate the                                                           Anaphase B
  daughter chromosomes at anaphase




                                                                                                                                               metaphase




                                                      Two models                                                                  Late anaphase

      Anaphase A: kinetochore microtubules and associated proteins             Anaphase B: Overlapping microtubule sliding force (kinesin)
                                                                               Astral microtubule (dynein)




                                                                                Microtubules of the mitotic spindle
                        Cytokinesis                                         determine the plane of animal cell division
• Most cells                                                                • Mitotic spindle
  – Cytokinesis follows                                                        – Contractile ring form
    mitosis                                                                      at the plane of
• Some cells                                                                     metaphase plate, at
                                                                                 the right angel to the
  – No cytokinesis, only                                                         long axis of the
    mitosis                             Cleavage in a fertilized frog egg
                                                                                 mitotic spindle
     • Osteoclast
                                                                               – Astral microtubules                       Microtubule asters determine the
     • Drosophila embryos                                                                                                         plane of cleavage
                                                                               – Overlapping
                                                                                 microtubules




                                                                                                                                                              4
               Asymmetric division                                                         Actin and myosin II in the contractile ring
                                                                                               generate the force for cytokinesis
• Some cells divide
  asymmetrically
                                                                                       • Use a similar
    – Different size and
      different cytoplasmic                                                              mechanism to that used
      contents                                                                           by smooth muscle cells
    – Crucial in controlling                                                                – Ca++-calmodulin activate
      tissue morphology                                                                       myosin light chain kinase
    – Particularly important in                                                               to phosphorylate myosin
      plants                                                                                  II
    – Some of the proteins                                                                                                                actin
      required for the
                                                                                       • Microtubules stabilize
      asymmetrical division                    Asymmetrical division of a fertilized     the ring
      have been identified                       egg of the nematode C. elegans
      through genetic analyses                                                                                                            Myosin II
      in the nematode C.
      elegans and Drosophila
      (chapter 21)
                                                                                                                          A dividing slime mold amoeba




                                                                                            Membrane-enclosed organelles must be
                            midbody                                                          distributed to daughter cells during
                                                                                                          cytokinesis
  • Overlapping                                                                        • Membrane-enclosed organelles
    microtubules                                                                         – Mitochondria and Chloroplasts
  • Dense matrix
                                                                                            • Large numbers present in cells
  • Residual midbody
                                                                                            • Double once each cycle
    remain on the inside of
    the plasma membrane                                                                • Endoplasmic reticulum and Golgi apparatus
    of each cell                                                                         – Organelle fragments (ER and Golgi)
      – May be important in                                                                associated with spindle microtubules via
        orient the spindle in the                                                          motor proteins, thereby hitching a ride to
        subsequent cell division
                                                                                           daughter cells




               Mitosis without cytokinesis                                                              Phragmoplast
                                                                                       • Phragmoplast
                                                                                            – Overlapping microtubules
                                                                                            – Vesicles derived from
                                                                                              Golgi apparatus
                                                                                            – Polysaccharide and
                                                                                              glycoproteins
Mitosis without cytokinesis in the Drosophila embryo (cellularization)
                                                                                       •    Cytokinesis in plants
                                                                                       •    No astral microtubule
                                                                                       •    No centrosomes
                           Multiple mitotic spindles before cellularization
                                                                                       •    Assembly of the cell
                                                                                            plate, guided by a
                                                                                            structure called
                                                                                            phragmoplast




                                                                                                                                                         5
                                                                                     Cell division in prokaryotic cells
 Cytokinesis in a higher plant cell                                                  Bacterium E. coli

                                                                                                           FtsZ protein (cytoskeletal GTPase, tubulin)




                                                                                      Binary fission




                                           alga




                                            protozoa




                                                                                                         Summary
                                                                                      • Nuclear division (mitosis)
                                                                                         – Bipolar mitotic spindles
                                                                                            • Centrosomes
                                                                                            • Microtubules: controlled by the balance
                                                                                              between MAPs and catastrophins
                                                                                               – Kinetochore microtubules
                                                                                               – Overlapping microtubules
                                                                                               – Astral microtubules
                                                                                            • Microtubule dependent motor proteins
Nuclear division occurs synchronously in a Drosphila embryo before cellularization
                                                                                            • Other proteins




                                                                                                                                                         6
              Summary (Cont’d)

• Cytoplasmic division (cytokinesis)
   – Mammalian cells and eukaryotes
      • Contractile ring
         – Actin
         – Myosin filaments
   – Plants
      • Phragmoplast
         – Overlapping microtubules
         – Vesicles derived from Golgi
         – Polysacchrides and glycoproteins




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