Why Do Cells Need a Cytoskeleton How do cells move vesicles and themselves CH 15 and 16 1031 and 113

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Why Do Cells Need a Cytoskeleton?How do cells
move vesicles and themselves?CH 15 and 16
10/31 and 11/3

• Cytoskeletal Components microtubules,
  microfilaments and intermediate fibers
• Cytoskeleton is required by all eukaryotic cells!
• Microtubule functions/characteristics
• Microfilament functions/characteristics
• Intermediate filament functions/characteristics
• Calcium, Actin and Myosingt contraction
• Skeletal and Cardiac Muscle VS. Smooth Muscle
• Intermediate assembly and hair

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Cells must respond to stresses and changes in
shape, they must also perform intracellular
mechanical work.

• Work Requires Structure for Leverage
• Exocytosis/Endocytosis/Vesicle Transport
• Shape changes and morphogenesis
• Nuclear and cellular division
• The Cytoplasm has 3 types of filament
• 1-Microtubules 25nm diameter-Largest subunit
  type
• Movement in the cell
• Tubulin alpha/beta subunits
• 2-Microfilaments 8 nm diameter- Smallest subunit
  type
• Movement of the cell
• G-actin subunits
• 3-Intermediate Filaments 8-12 nm
  dia-Intermediate size
• Structural support in/around cell
• Tissue specific proteins
• These 3 filaments function to create an
  intracellular matrix for organization, attachment
  and intracellular motion.

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Microtubules consist of tubulin protein dimers (a
and B) that guide intracellular transport
vesicles and proteins to the proper location
within a cell.

• Sites of Special Importance
• 1-Formation of Mitotic Spindle
• One Kinetochore for each chromosome
• Chromosomes microtubule elongation separates the
  chromosomes at anaphase
• 2- Guiding Vesicles exocytosis/endocytosis
• Clathrin is important especially in endocytosis
• 3-Critical for axoplasmic flow in axons/dendrites
• Carry vesicles with NT to axon or recycle NT to
  nucleus
• 4- Important to structure of flagella and cilia
• -92 pattern of microtubules
• 5- Inhibiting tubule synthesis kills cell
  (antimitotic)!
• Cancer Drugs Vinblastine no MT formed
• Taxol MT not disassembled for division

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How are microtubules made at specific nucleation
cites? Alpha/Beta monomers? Dimers?Tubes(25nm
dia) Tubulin-GTP is added at the positive end of
the tube and removed from the negative end of
tube.
XXX
XXX
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What events inside a cell are dependent upon
proper the formation/destruction of microtubules
(MTs) at locations called microtubule organizing
centers (MTOCs)?
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Dynein and Kinesin proteins crawl along
microtubules and carry vesicles with them using
ATP as the energy source.Dynein moves toward
Negative Direction.Kinesin moves toward
Positive DirectionSimilar proteins form the
radial spokes of flagella and cilia.
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Dynein and kinesin proteins can be active at the
same time and move vesicles in opposite
directions (- or ) on the same microtubules!
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Flagella and Cilia Dynein arms move across
adjacent MTs causing sliding/axoneme bending
motion
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Visualization of Dynein/ATP-dependent sliding
action across adjacent axonemes in a flagella. In
terms of the ATP that drive this process, why do
sperm carry mitochondria? Where do your
mitochondria come from? How could a genetic
defect in dynein result in linkage of male
sterility and respiratory disease?
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Microfilaments are the smallest cytoskeletal
structures in the cell and form thread-like actin
structures in the cytosol.

• Important for muscle contraction (actin/myosin)
• Important for ameboid motion/cytoplasmic
  streaming
• Organization
• Monomers of G-actin-ATP polymerize into long
  strands of F-actin (mature actin)
• Small about 7 nm in diameter
• Strands form a double helix
• Some strands become cross-linked by filamin for
  extra strength!

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Microfilaments are primarily formed by adding
G-actin to the positive fast-growing end of the
filament.Actin polymerization requires ATP, K
and MgWhat effect does the drug cytochalasin
have?
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Microfilaments can form diffuse gel-like matrices
OR they can become tightly cross-linked to form
rigid structures like the non-motile microvilli
found on intestinal epithelial cells.
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Microfilaments can also be linked to proteins in
the plasma membrane and molecules/materials
outside the cell itself by N-CAMS. This is
important for attaching the brush border of the
mucus membrane to the cell!

• Classic Link
• Protein Types
• Ankyrin
• Spectrin
• Band 4.1

Microtubule of G-actin monomers
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Myosin-II forms large polymers (2H 4L) for
muscle contraction. Myosin-I monomers attach
actin to plasma membranes, moving vesicles, and
pushing actin rods in the direction of cell
elongation (have you ever seen a pseudopod on an
amoeba?).
These are examples of Myosin-I Monomers actin
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Depolarization of the target cell occurs when the
ACH in a vesicle is released (exocytosis),
diffuses across synapse, and binds/open its
receptor (a Ligand Gated-Na Channel)? This
should be review.
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End Plate Potential One exocytosis may not
release enough ACH to open enough ligand-gated
channels to create enough depolarization to cause
enough depolarization to open the voltage gated
channels. Membrane potential changed, but not
enough for Na-VGC threshold to be reached. Wait
till next exocytosis of ACH to occur.
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Review of structural organization
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Smooth muscle cells are found in blood vessels,
glands, guts,and other places. SMCs contract
using calcium entry/calmodulin binding as a
signal to activate myosin light chain kinase
(MLCK). MLCK phosphorylates myosin letting it
bind actin and contract.
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Once the myosin in smooth muscle is
phosphorylated it binds actin and the cell
contracts, contraction ends when Ca leaves the
cell and MLC-phosphatase removes the phosphate
from MYOSINleading to SMC relaxation
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Intermediate Filaments (polymers) consist of
relatively tissue specific proteins and are
transcribed from genes only expressed in specific
tissues.

• Classics
• Desmosones and Hemidesmosomes
• Mechanical strength to the cell wall-
• Cellular glue!
• Keratins
• Mechanical strength to epithelial cells
• Form skin and hair!
• Desmin
• Attachment of actin from myosin complex to Z-line
  of cell end plate! STRONG!
• Neurofilaments
• Provide strength to the long fragile axons of
  body!
• Tangles are one of the prime indicators/causes
  of the cellular dysfunction that leads to
  Alzehimers disease

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How are intermediate filaments assembled?
Monomer?Dimer?Tetramer?Protomer?Filament (8-10
nm diameter)
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Hair is formed when epithelial cells in a hair
follicle accumulate keratin and die. New cells
push the old ones out and you have hair growth!
Curls in hair are created when the
disulfide-cross links dont match-up evenly!
Perms modify this artificially!