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The Cell Cytoskeleton 1
The Cell Cytoskeleton Chapter 17
Questions in this chapter you should be able to answer:
Chapter 17: 1 - 11, 13 - 23
Watch this animationhttp://multimedia.mcb.harvard.edu/ anim_innerlife.html
The Inner Life of Cells
Tick and Sick - 8 2
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
The Cell Cytoskeleton 3
The Cell Cytoskeleton
What are the 3 primary typesof cytoskeletal proteins?
Intermediate filaments-- resist mechanical stress
Microtubules-- cytoplasmic transport-- axoneme movement -- chromosome movement
Actin filaments-- membrane contraction
-- muscle cells-- cytokinesis
-- cell movements
The Cell Cytoskeleton 4
What is the structure of intermediate filamentsCable-like arrangement
Extended molecular interactions
Anchoring to desmosomes
Intermediate Filaments
Tick and Sick - 8 5
Intermediate filaments -- help hold cells & tissues together
Human lung carcinoma
Tick and Sick - 8 6
Intermediate filaments also occur in the nucleus
Cytoplasmic -- keratins – skin integrity -- in neurons -- in muscle, connective tidssue
Nuclear -- lamins
Tick and Sick - 8 7
Microtubules & Actin filaments make possible different types of movements
Cell migrationNeutrophil Flagella and cilia
Cytoplasmic movementsMuscle contractionMitosis and Cell divisionCytoplasmic transport
Membrane movements Membrane ruffling
Tick and Sick - 8 8
Helps to distribute materials through the cell
This highway is ‘dynamic’
Cytosolic Microtubules
Tick and Sick - 8 9
The ‘spindle apparatus’ controls chromosome movements
-- Attached to “kinetochores” on duplicated chromosome
Spindle ApparatusKinetochore function
Cell Division
The Cell Cytoskeleton 10
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
Tick and Sick - 8 11
Kinesin walking
Motor proteins carry “cargo” along microtubules
Two motor proteins
Opposite directions
How does Kinesin ‘walk”?
Organelle movement
Kinesin walking
Organelle movement
The Cell Cytoskeleton 12
What is the mechanism of MT growth and retraction?
Binding, hydrolysis and release of GTP
‘Capping’ at cell membrane
Question 17-3, p 583
How would a change in [tubulin] affect MT dynamics?
..if only GDP were present?
… or a nonhydrolizable GTP analog?
MT with EB1 cap
The Cell Cytoskeleton 13
What is the structure and movement of an axoneme?
Cilia & flagella
“9 + 2 Structure”
Living Cell video
Tick and Sick-1 14
Where are human cilia and flagella found?
Various places
Some genetic conditionscause cilia not to function
Symptoms of IMSRespiratory infection;
Fertility problems Etc…
and ‘situs inversus‘’ (50%)
Respiratory cilia
Tick and Sick-1 15
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
Tick and Sick-1 16
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
The Cell Cytoskeleton 17
What is the distribution and structure of actin filaments?
treadmilling
The Cell Cytoskeleton 18
How are actin filaments organized in the cytoplasm?
The cell cortex
Actin binding proteins
The Cell Cytoskeleton 19
How does actin mediate cell movements?
Cell crawling
What are Lamellipodia and Filopodia?
Membrane ruffling
Listeria movement
Tick and Sick - 8 20
Actin Filaments are involved in muscle contraction
What happens when muscles contract?
Nerve impulses activate contraction at neuromuscular junction
Tick and Sick - 8 21
What is structure of muscle cells?
Some basic anatomy. . .
“Muscles” are bundles of muscle cells
Sarcomeres -- are the smallest contractile unit of muscles
Tick and Sick - 8 22
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
Tick and Sick - 8 23
Sarcomeres create visual ‘striations ‘of “Striated muscles” (skeletal muscles)
Tick and Sick - 8 24
Muscle spasms and cramps (“Charley Horse”)
Imbalance in excitatory and inhibitory signals-- self-reinforcing cycle occurs
The Cell Cytoskeleton 25
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
How does the sliding filament model explain sarcomere contraction?
myosin
The Cell Cytoskeleton 26
How is muscle contraction triggered?
Motor neuron & action potential
Sarcoplasmic reticulum
T-tubules
Ca++ release
The Cell Cytoskeleton 27
How does Ca++ trigger the muscle contraction?
The tropomyosin / troponin complex
Sarcomere
The Cell Cytoskeleton 28
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?