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Announcements. Please remove exam answer sheets, homework from your folders. News story on “semi-identical twins” posted on Blackboard. Today, April 4: microtubules, pp. 425-437 Friday, April 6: Microtubules and microfilaments, pp. 425-446 (742-762 in 5 th Ed.) - PowerPoint PPT Presentation
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Announcements
• Please remove exam answer sheets, homework from your folders.
• News story on “semi-identical twins” posted on Blackboard.
• Today, April 4: microtubules, pp. 425-437• Friday, April 6: Microtubules and
microfilaments, pp. 425-446 (742-762 in 5th Ed.)
• Monday, April 9: Muscle contraction, Cell motility, intermediate filaments.
Exam 3 Results
• Key and full standings posted outside BR 179• Average before curve = 45/72 = 63%• Average after curve = 58/72 = 80%
– 13 points added to everyone’s raw score to curve• High = 87/72 (120%)
90-100% (>=65): 1680-89% (58-64): 770-79% (50-57): 960-69% (43-49): 9<60% (<43): 5
• Do add up your raw score, count the number correct, multiply by 3, add any extra credit then add 13 points.
Outline/Learning Objectives
I. MicrotubulesA. Structure and
assemblyB. Dynamic instability
modelC. Microtubules in motionII. Microfilaments
A. Video of MF-based motility
B. Actin and assembly
After reading the text, attending lecture, and reviewing lecture notes, you should be able to:
• Compare and contrast microtubules, microfilaments and intermediate filaments.
• Describe microtubule structure and assembly/disassembly, including nucleation and dynamic instability. Explain the function of MAPs, kinesin, and dynein.
• Explain how axonemal structure determines ciliary movement.
• Describe microfilament structure and assembly.
• Give examples of microfilament-based motility.
Semi-identical twinsSouter et al. 2007
RSTK Pathway
• Another class of growth and differentiation factors signal through receptor serine-threonine kinases.
• E.g. TGFβ• Many involved in
development• Smad transcription
factors become active when phosphorylated.
Steps of apoptosis, or programmed cell death
• Examples: normal cell senescence, damaged/infected cells, embryonic digits, tadpole tails, pruning of infant neurons.
Apoptosis Pathway
• Programmed cell death discovered in nematode C. elegans.
• Present in other organisms, e.g. mammals.
• Triggered either by presence of death factors or removal of survival factors.
(a) killer lymphocytesacting on infected cells
(b) removal ofsurvival factors/DNA damage
Components and Functions of the Cytoskeleton
Recent review: Pollard, T.D. (2003). Nature 422:741-745.
Self-assembly of cytoskeletal filaments
• Polymerization does not involve covalent bonds, rather weak interactions between monomers.– Therefore, can assemble or disassemble rapidly,
without covalent bond formation or breaking.
• Combine strength with adaptability through lateral interactions in addition to length-wise interactions.
• Nucleation is rate-limiting step of polymerization
Microtubules
• Cytoplasmic MTs:– dynamic growth and
collapse– in nerve processes,
mitotic spindles, elongating cells, etc.
• Axonemal MTs:– stable– in cilia, flagella
• http://raven.zoology.washington.edu/celldynamics/
Videos: Microtubules in Motion
1. Interphase microtubules: dynamic instability
2. Chromatophores: pigment granule transport along microtubules
3. Axopodia in Heliozoans: prey capture and transport along microtubules
4. Mitosis in animal, plant cells
Microtubule Structure
• 25 nm outer diameter• 12 protofilaments, polymers of
heterodimeric and -tubulin (50 kD each). -tubulin binds GTP
• Destabilized by:– cold, pressure– Drugs colchicine, nocodazole, etc.– > 10-6 M Ca2+
• Stabilized by:– Drug taxol– MT-associated proteins (MAPs)
Centrosomes organize cytoplasmic MTs
• Animal centrosomes contain two centrioles (9 short triplet MTs), plant centrosomes don’t.
• Pericentriolar material nucleates MTs (animals and plants) (gamma)-tubulin– pericentrin
• Minus end of MT starts in centrosome, plus end is away.
Microtubule organization in cells
Dynamic Instability of MTs:
GTP cap stabilizes + end
of MTs
Recent review: Howard and Hyman. (2003). Nature 422:753-758.
Microtubule Poisons(and Anti-Cancer Drugs)
• Colchicine– Alkaloid from meadow saffron– Binds tubulin monomers, prevents
assembly processes that require assembly are blocked
– Colcemid, nocadazole, etc. also (-) assembly
• Taxol– Alkaloid from Pacific yew tree,
effective chemo- in ovarian cancer– Can now be synthesized in vitro– Binds microtubules, stabilizes,
prevents disassembly processes that require disassembly are blocked
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