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CHAPTER 16 THE
CYTOSKELETON• THE SELF-ASSEMBLY AND DYNAMIC STRUCTURE OF CYTOSKELETAL FILAMENTS
• HOW CELLS REGULATE THEIR CYTOSKELETAL FILAMENTS
• MOLECULAR MOTORS
• THE CYTOSKELETON AND CELL BEHAVIOR
THE SELF-ASSEMBLY AND DYNAMIC
STRUCTURE OF CYTOSKELETAL FILAMENTS
• Three Types of Cytoskeletal Filaments
• Nucleation Is the Rate-limiting Step in the Formation of a Cytoskeletal Polymer
• The Two Ends of a Microtubule and of an Actin Filament Are Distinct and Grow at Different Rates
• Filament Treadmilling and Dynamic Instability Are Consequences of Nucleotide Hydrolysis by Tubulin and Actin
• Intermediate Filaments Impart Mechanical Stability to Animal Cells
• Filament Polymerization Can Be Altered by Drugs
Three Types of Cytoskeletal Filaments
• Actin filaments (5-9 nm diameter)
– Actin subunits
– Locomotion, muscle contraction
• Intermediate filaments (10 nm diameter)
– Various coiled coil protein subunits
• (lamins, vimentin, keratin)
– Structural roles
• Microtubules (25 nm diameter)
– Tubulin subunits
– Intracellular transport
Nucleation Is the
Rate-limiting
Step in the
Formation of a
Cytoskeletal
Polymer
The Two Ends of
Microtubules
and Actin
Filaments Are
Distinct and Grow at Different
Rates
Filament Treadmilling and Dynamic Instability Are
Consequences of Nucleotide Hydrolysis
Tubulin -
dynamic
instability
Intermediate
Filaments
Impart
Mechanical
Stability to
Animal Cells
Filament Polymerization Can Be
Altered by Drugs• TABLE 16–2 Drugs That Affect Actin Filaments and Microtubules
• ACTIN-SPECIFIC DRUGS– Phalloidin binds and stabilizes filaments
– Cytochalasin caps filament plus ends
– Swinholide severs filaments
– Latrunculin binds subunits and prevents their polymerization
• MICROTUBULE-SPECIFIC DRUGS– Taxol binds and stabilizes microtubules
– Colchicine, colcemid binds subunits and prevents their polymerization
– Vinblastine, vincristine binds subunits and prevents their polymerization
– Nocodazole binds subunits and prevents their polymerization
HOW CELLS REGULATE THEIR
CYTOSKELETAL FILAMENTS
• Microtubules Are Nucleated by a Protein Complex Containing γγγγ-tubulin in the Centrosomes of Animal Cells
• Regulatory Proteins Bind to Free Subunits, Filaments Sides and Filament Ends
• Extracellular Signals Can Induce Major Cytoskeletal Rearrangements
Microtubules Are Nucleated by a
Protein Complex Containing γγγγ-tubulin
in the Centrosomes of Animal Cells
Regulatory Proteins Bind to Free Subunits,
Filaments Sides and Filament Ends
Extracellular
Signals Can
Induce Major
Cytoskeletal
Rearrangements
MOLECULAR MOTORS
• Actin-based Motor Proteins Are Members
of the Myosin Superfamily
• There Are Two Types of Microtubule Motor
Proteins: Kinesins and Dyneins
• Motor Proteins Generate Force by
Coupling ATP Hydrolysis to
Conformational Changes
• Cilia and Flagella Are Motile Structures
Built from Microtubules and Dyneins
Actin-based Motor Proteins Are
Members of the Myosin Superfamily
• Myosin II is the
muscle motor
• Other myosins
have other
functions
There Are Two Types of Microtubule
Motor Proteins: Kinesins and Dyneins
Motor Proteins
Generate Force by
Coupling ATP
Hydrolysis to
Conformational
Changes
Different motors can run in
opposite directions
Cilia and Flagella Are Motile Structures
Built from Microtubules and Dyneins
THE CYTOSKELETON AND
CELL BEHAVIOR
• Mechanisms of Cell Polarization Can
Be Readily Analyzed in Yeast Cells
• Directional Assembly Dictates the
Direction of Cell Migration
• The Complex Morphological
Specialization of Neurons Depends
on The Cytoskeleton
Mechanisms of Cell Polarization Can Be Readily
Analyzed in Yeast Cells
Signal transduction pathway to
polymerization
Directional Assembly Dictates the Direction
of Cell Migration
The Complex Morphological Specialization of
Neurons Depends on The Cytoskeleton
CHAPTER 18 THE
MECHANICS OF CELL
DIVISION
• AN OVERVIEW OF M PHASE
• MITOSIS
• CYTOKINESIS
AN OVERVIEW OF M PHASE
• Cohesins and Condensins Help Configure Replicated Chromosomes for Segregation
• The Cytoskeleton Carries Out Both Mitosis and Cytokinesis
• Two Mechanisms Help Ensure That Mitosis Always Precedes Cytokinesis
• M Phase Depends on DNA Replication and Centrosome Duplication in the Preceding Interphase
• M Phase Is Traditionally Divided into Six Stages
Cohesins and Condensins Help Configure
Replicated Chromosomes for Segregation
The Cytoskeleton Carries Out Both Mitosis
and Cytokinesis
Two Mechanisms Help Ensure That Mitosis
Always Precedes Cytokinesis
• 1. Proteins required for cytokinesis are
inactivated by M-Cdk during mitosis
• 2. The remnants of the mitotic spindle are
required for assembly of the contractile ring
before cytokinesis
M Phase Depends on DNA Replication and Centrosome
Duplication in the Preceding Interphase
M Phase Is Traditionally Divided into Six Stages
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis
MITOSIS
• Microtubule Instability Increases Greatly at M Phase
• Interactions Between Opposing Motor Proteins and Microtubules of Opposite Polarity Drive Spindle Assembly
• Kinetochores Attach Chromosomes to the Mitotic Spindle
• Anaphase Is Delayed Until All Chromosomes Are Positioned at the Metaphase Plate
• Sister Chromatids Separate Suddenly at Anaphase
• Kinetochore Microtubules Disassemble at Both Ends During Anaphase A
• Both Pushing and Pulling Forces Contribute to Anaphase B
• At Telophase, the Nuclear Envelope Re-forms Around Individual Chromosomes
Mitotic
Machinery
Microtubule Instability Increases Greatly
at M Phase
• MAPs stabilize
• Catastrophins destabilize
• Rapid turnover results in survival of only productive (capped, attached, stabilized) microtubules
Interactions Between Opposing Motor Proteins and
Microtubules of Opposite Polarity Drive Spindle Assembly
• (-) end motors (like Kar3p)
organize tubules at spindle poles
• (+) end motors (like Cin8p) push
tubules of opposite orientation
against each other
Kinetochores Attach Chromosomes to the
Mitotic Spindle
Sister Chromatids Separate
Suddenly at Anaphase
Both Pushing
and Pulling
Forces
Contribute to
Anaphase B
CYTOKINESIS
• The Microtubules of the Mitotic Spindle Determine the Plane of Animal Cell Division
• Actin and Myosin II in the Contractile Ring Generate the Force for Cytokinesis
• Membrane-enclosed Organelles Must Be Distributed to Daughter Cells During Cytokinesis
• Mitosis Can Occur Without Cytokinesis
• The Phragmoplast Guides Cytokinesis in Higher Plants
• The Elaborate M Phase of Higher Organisms Evolved Gradually from Procaryotic Fission Mechanisms
The Microtubules
of the Mitotic
Spindle
Determine the
Plane of Animal
Cell Division
Actin and Myosin II in the Contractile Ring
Generate the Force for Cytokinesis
Bacterial Fission - a
model for M phase
& FtsZ - a bacterial
tubulin homolog