Transcript What is the Cell Cytoskeleton?

The Cell Cytoskeleton
Chapter 17
Watch this animation
http://multimedia.mcb.harvard.edu/
anim_innerlife.html
The Inner Life of Cells
Questions in this chapter you should be able to answer:
Chapter 17: 1 - 11, 13 - 23
The Cell Cytoskeleton
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All of these movements are made
possible by the cell “Cytoskeleton”
What is the Cell Cytoskeleton?
-- long protein filaments
-- extend through the cytoplasm
A variety of purposes
Three families
• Microtubules
• Actin filaments
• Intermediate filaments
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The Cell Cytoskeleton
What are the 3 primary types
of cytoskeletal proteins?
Intermediate filaments
-- resist mechanical stress
Microtubules
-- cytoplasmic transport
-- axoneme movement
-- chromosome movement
Actin filaments
-- membrane contraction
-- muscle cells
-- cytokinesis
-- cell movements
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What is the structure of intermediate
filaments
Cable-like arrangement
Extended molecular interactions
Anchoring to desmosomes
Intermediate
Filaments
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Intermediate filaments
-- help hold cells & tissues together
Human lung carcinoma
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Intermediate filaments also occur in the nucleus
Cytoplasmic
-- keratins – skin integrity
-- in neurons
-- in muscle, connective tidssue
Nuclear -- lamins
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Microtubules & Actin filaments make
possible different types of movements
Cell migration
Neutrophil
Flagella and cilia
Cytoplasmic movements
Muscle contraction
Mitosis and Cell division
Cytoplasmic transport
Membrane movements
Membrane ruffling
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Cytosolic Microtubules
Helps to distribute materials
through the cell
This highway is ‘dynamic’
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The ‘spindle apparatus’ controls chromosome
movements
-- Attached to “kinetochores” on duplicated chromosome
Cell Division
Kinetochore function
Spindle Apparatus
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What is the fundamental structure of
microtubules?
Alpha and beta tubulin subunits
13 member ring
Why do MTs have polarity?
‘MT Organizing Center’
Why are MTs said to display ‘Dynamic
Instability’?
Dynamic Instability
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Motor proteins carry “cargo”
along microtubules
Two motor proteins
Opposite directions
Kinesin walking
How does
Kinesin ‘walk”?
Kinesin walking
Organelle movement
Organelle movement
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What is the mechanism of MT
growth and retraction?
Binding, hydrolysis and release of GTP
‘Capping’ at cell membrane
MT with EB1 cap
Question 17-3, p 583
How would a change in [tubulin]
affect MT dynamics?
..if only GDP were present?
… or a nonhydrolizable GTP analog?
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What is the structure
and movement of an
axoneme?
Cilia & flagella
“9 + 2 Structure”
Living Cell video
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Where are human cilia
and flagella found?
Various places
Respiratory cilia
Some genetic conditions
cause cilia not to function
Symptoms of IMS
Respiratory infection;
Fertility problems
Etc…
and ‘situs inversus‘’ (50%)
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An interesting congenital genetic disorder
-- “Immotile Cilia Syndrome”
Symptoms:
•
•
•
•
Respiratory tract infections
Infertility
Digestive problems
Situs Inversus
-- Affects ~50% of people with IMS
- IDA
- ODA
- IDA
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What is the link between cilia
and Left/Right orientation?
Cilia occur in the “embryonic node”
-- very early stage of development
Generate oriented flow
of signal molecule
Why 50% affected?
Embryonic node cilia
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What is the distribution and
structure of actin filaments?
treadmilling
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How are actin filaments
organized in the cytoplasm?
The cell cortex
Actin binding proteins
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How does actin mediate cell
movements?
Cell crawling
What are Lamellipodia and Filopodia?
Membrane ruffling
Listeria movement
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Actin Filaments are involved
in muscle contraction
What happens when muscles
contract?
Nerve impulses activate contraction
at neuromuscular junction
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What is structure of muscle cells?
Some basic anatomy. . .
“Muscles” are bundles
of muscle cells
Sarcomeres
-- are the smallest
contractile unit of muscles
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Some details of Sarcomeres,
Actin and Myosin…
Nerve impulse triggers
Ca++ release Inside of cell
-- Myosin pulls on actin
-- Pulls sarcomere shorter
Ca++ quickly removed
-- leads to relaxation
Muscle contraction
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Sarcomeres create visual ‘striations ‘of
“Striated muscles” (skeletal muscles)
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Muscle spasms and cramps (“Charley Horse”)
Imbalance in excitatory and inhibitory signals
-- self-reinforcing cycle occurs
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How does the sliding
filament model explain
sarcomere
contraction?
Myosin is attached
ATP binds
-- Myosin head detaches
ATP is hydrolyzed
-- Myosin Head cocks
-- loosely binds to actin
Pi is released
-- which triggers ….
Powerstroke
-- during which…
ADP is released
Myosin remains attached
myosin
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How is muscle contraction triggered?
Motor neuron &
action potential
Sarcoplasmic reticulum
T-tubules
Ca++ release
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How does Ca++ trigger the muscle contraction?
The tropomyosin / troponin complex
Sarcomere
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Question
In order to keep cytosolic Ca++ levels low, muscle cells possess an ATP driven
Ca++ pump in the sarcoplasmic reticulum and a Ca++/Na+ ATPase in the cell
membrane. The cells also possess the Na+/K+ ATPase in the cell membrane.
The Na+/K+ ATPase is partially inhibited by drugs such as ouabain and digitalis,
whereas the Ca++/Na+ ATPase is inhibited by binding to a protein called
phospholamban.
A. Draw a diagram showing the expected arrangement and orientation in the
membranes of these membrane proteins.
B. Would treating a patient with either of these drugs weaken or strengthen
muscle contraction (they are usually given to cardiac patients)? Explain.
C. The regulatory protein “protein kinase C” (PKC) regulates activity of the
Ca++ ATPase. PKC can phosphorylate (covalently add a PO4) to the Ca++
ATPase, which increases its affinity for Ca++. What would be the expected
effect of Ca++ ATPase phosphorylation on the strength of muscle contraction?
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