• main component = Microtubules
  • different MAPS (kinesin-related proteins
  • dynein
  • regulatory proteins present
• Dynamic properties of MTs
  • ability to polymerize and depolymerize
  • ability to bind motor proteins

colchicine = depolymerizing agent for MTs

Taxol = stablilizing agent

(anti-mitotic) interfere w/normal operation of cell spindle/block cell division

Centrosomal defects produce:

• Spindle abnormalities
• Chromosome missagregation
• Aneuploidy
  • Produce imbalance between growth-promoting oncogenes and growth-regulating tumor supressor genes--->leading to cancer
• Also could contribute to disruption in overall cellular architecture

3 type of MT in fully formed Mitotic spindle

1. Interpolar microtubles
   1. Extend from two poles of spindle toward equator
   2. Most  numerous of Mts
   3. Overlap w/ polar fibers of other pole

1. Kinetochore microtubules
   1. Attached to kinetochore structure of chromatids/extend toward spindle poles

1. Astral microtubules
   1. Radiate out of spindle poles towards membrane

-involved in chromosome condensation during prophase

-phosphorylates elements in nuclear pore complex/nuclear lamina

--->triggers nuclear envelope breakdown in prometaphase

Organize the spindle in early mitosis

-is an active process

-both (+) and (-) end directed MT motors are involved in pushing, pulling and sliding until poles are properly positioned at opp. sides of cell and chromosomes in center.

-involved in spindle pole formation

- (-) end directed motors is involved in consolidating normal "football-like" shape of spindle

Kinetochore

-specialized attachment site for microtubules at the centromere

-develops during late prophase

-Kinetochore MTs have (+) ends in proximity to Kinetochore

-Centomeric (CEN)DNA generates kinetechore

Balancing forces on metaphase spindle

-cytosolic dynein at kinetochore pulls chromosomes to pole

-chromokinesins (4,10) exerts opposite force and pushes them away from poles

Only after all kinetochores are captured and the chromosomes are aligned on the equator will the cell initiate anaphase.

-half of mitosis is spent in metaphase.

-very dramatic action phase, but is SHORTEST part

-chromosomes separate and move to the poles and then the poles move apart

-cell lenghtens in preparation for cytoplasmic division (cytokinesis)

-cohesion complexes that connect chromatids along lengths, are cleaved

-->degradation of inhibitor to protease occurs

-->involves increase in cytosolic calcium

APC targets inhibitory protein securin for degradation.

securin binds/inhibits activity of separase

securin destroyed; releases separase, cleaves cohesin.

-reformation of nuclear envelope

-decondensation of chromosomes occurs

Anaphase A: chromatids move toward pole and kinetochore MTs shorten

--->active MT disassembly

Motor proteins are NOT involved, absense of ATP

Anaphase B: spindle elongates and poles of spindle move further apart.

--->MT growth at + ends of Polar MT

--->depends on motor proteins located at central spindle

two phases show differential sensitivity to various drugs/inhibitors

-requires function of contractile ring of actin-myosin to separate the daughter cells

-involves actin/myosin II interactions

-begins in Anaphase continues through Telophase and into Interphase