Lecture 27 Cytoskeleton.pptx

Lecture 27
Cytoskeletal System
Chapter 13
4 - 1-2022
Lecture 27, Cytoskeleton

Antimitotic Drugs
• These drugs are called antimitotic drugs
because they interfere with spindle assembly
and thus inhibit cell division.
• They are useful for cancer treatment
(vinblastine, vincristine) because cancer cells
are rapidly dividing and susceptible to drugs
that inhibit mitosis.
© 2017 Pearson Education, Ltd.

Taxol
• Taxol binds tightly to microtubules and
stabilizes them, causing a depletion of free
tubulin subunits.
• It causes dividing cells to arrest during
mitosis.
• It is also used in cancer treatment, especially
for breast cancer

Drugs can affect the assembly of
microtubules - taxol
1. from bark of Western Yew
2.binds beta tubulin
3.Stabilizes microtubules
4.stimulates free tubulin to form microtubules
5.arrests dividing cells in mitosis
6.spindle Mts don't breakdown

Taxol stabilizes MTs and prevents cell division

Dynamic Instability
• Dynamic instability model: one population
of MTs grows by polymerization at the plus
ends, whereas another population shrinks by
depolymerization.
• Growing MTs have GTP at the plus ends, and
shrinking MTs have GDP.
• The GTP cap at the plus end prevents
subunit removal

GTP Hydrolysis Contributes to the Dynamic
Instability of Microtubules
• Each tubulin heterodimer binds two GTP
molecules; α-tubulin binds one, and β-tubulin
binds a second.
• The GTP bound to the β-subunit is hydrolyzed to
GDP after the heterodimer is added to the MT.
• GTP is needed to promote heterodimer
interactions and addition to MTs, but its
hydrolysis is not required for MT assembly

Growing MTs have GTP cap
at + end
ECB 17-13
GTP cap regulates MT dynamics

Microtubules Originate from Microtubule-
Organizing Centers Within the Cell
• MTs originate from a microtubule-organizing
center (MTOC).
• Many cells have an MTOC called a centrosome
near the nucleus.
• In animal cells, the centrosome is associated with
two centrioles surrounded by pericentriolar
material

Microtubules radiate outward from (MTOCs)
12
MTOC = Mt organizing center
MTOC usually near nucleus
Microtubules radiate outward toward cell PM
Dynamic Mts with fluorescence

Centriole Structure
• Centriole walls are formed by nine pairs of triplet
microtubules.
• They are oriented at right angles to each other.
• They are involved in basal body formation for
cilia and flagella.
• Cells without centrioles have poorly organized
mitotic spindles

animal cell
centrosome
centrosome =
granular material
surrounding two
centrioles

Eukaryotic flagella and cilia are anchored to “basal
bodies”
Basal bodies
Flagellum
Outer
doublet
Central pair
MCB figure 19-29
Freeman Puiblishing

MBoC (4) figure 16-80
Basal bodies are 9+0 “cartwheels” of MT triplets
A
B
C
A and B subfibers in basal body are continuous with
A and B subfibers in cilium/flagellum
A
B
C

Eukaryotic flagella and cilia are
composed of MTs
Flagellar core is a “9+2” arrangement of microtubules
“Dynein arms” power sliding of MTs in outer doublets past
each other; result = bending of cilium/flagellum
Central pair, radial spokes etc. regulate sliding/bending
ECB 17-27
1
2
3
4
5
6
7
8
9
B A
B
A
“Inner arms”
Plasma membrane
“Outer doublets”
Central pair
Central sheath
Radial spokes
Nexin
“Outer arms”

Microtubule polarity
 Microtubules have inherent
polarity
 One end grows faster, (+) end,
farthest from cell center
 One end grows slower, (-) end,
closest to cell center

Microtubule-Stabilizing/Bundling
Proteins
• MAPs, microtubule-associated proteins, bind
at regular intervals along a microtubule wall,
allowing for interaction with other cellular
structures and filaments
– A MAP called Tau causes MTs to form tight
bundles in axons
– MAP2 promotes the formation of looser bundles
in dendrites

MAPs That Promote Bundling
• MAPs such as Tau and MAP2 have two regions.
• One region binds to the MT wall, and another
part of the protein extends at right angles to the
MT to allow for interaction with other proteins.
• The length of the extended “arm” controls the
spacing of MTs in the bundle

+–TIP Proteins
• MTs can be stabilized by proteins that “capture”
and protect the growing plus ends.
• These are +–TIP proteins (+–end tubulin
interacting proteins).
• Proteins such as EB1 (end-binding protein 1)
decrease the likelihood that MTs will undergo
subunit loss

Microtubule-Destabilizing/Severing
Proteins
• Some proteins promote depolarization of MTs
– Stathmin/Op18 binds to tubulin heterodimers
and prevents their polymerization.
– Catastrophins act at the ends of MTs and
promote the peeling of subunits from the
ends.
– Proteins such as katanin sever MTs

13.3 Microfilaments
• Microfilaments are the smallest of the
cytoskeletal filaments.
• They are best known for their role in muscle
contraction.
• They are involved in cell migration, amoeboid
movement, and cytoplasmic streaming

Additional Roles of Microfilaments
• Development and maintenance of cell shape (via
microfilaments just beneath the plasma membrane
at the cell cortex).
• Structural core of microvilli.

Actin Is the Protein Building Block of
Microfilaments
• Actin is a very abundant protein in all eukaryotic
cells.
• Once synthesized, it folds into a globular-shaped
molecule that can bind ATP or ADP (G-actin;
globular actin).
• G-actin molecules polymerize to form
microfilaments, F-actin

Different Types of Actin Are Found in Cells
• Actin is highly conserved, but there are some
variants.
• Actins can be broadly divided into muscle-
specific actins (α-actins) and nonmuscle actins
(β- and γ-actins).
• β- and γ-actin localize to different regions of a
cell

G-Actin Monomers Polymerize into
F-Actin Microfilaments
• G-actin monomers can polymerize reversibly
into filaments with a lag phase and elongation
phase, similar to tubulin assembly.
• F-actin filaments are composed of two linear
strands of polymerized G-actin wound into a
helix.
• All the actin monomers in the filament have the
same orientation.

Functions of microfilaments
 Muscle contraction
 Amoeboid movement
 Cell locomotion
 Cytoplasmic streaming
 Cell division
 Cell shape
Lecture 28 Cytoskeletal system 30

Microfilaments occur in most eukaryotic cells
Many cellular motions are based on microfilaments
a.Muscle contraction -eg: contractile fibrils shorten
b.Cytoplasmic streaming -eg: chloroplasts and other
inclusions "flow" around the vacuole in Elodea

Microfilaments occur in most eukaryotic cells
c) Cleavage furrows of dividing cells -eg:
cytokinesis
D) Development and maintenence of cell shape
-Eg: red blood cell have characteristic shape and
both microfilaments and microtubules are required
to keep the shape

“Non-muscle” actin is abundant in non-muscle cells
 Microvilli: “brush border” epithelia of intestine (increased
surface area).
Contractile ring
Microvilli
 Contractile ring: division of the cytoplasm in animal cells
 Cortical actin: just beneath plasma membrane of most
eukaryotic cells Lecture 28 Cytoskeletal system
33

“Non-muscle” actin is abundant in non-muscle cells
Microvilli: “brush border” epithelia of intestine
(increased surface area), “hair cells” of inner ear (sound
detection).
Stress fibers and
focal contacts
Microvilli
Adapted from ECB figure 17-29
Stress fibers: adhesion and cell shape (fibroblasts
growing in vitro).

Lecture 27 Cytoskeleton.pptx

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