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BIO 320
Summary of proteins that regulate the
organization of the Actin Cytoskeleton
Regulation of Actin Organization:
Nucleating Factors Arp2/3 & Formin (covered in class)
G-Actin binding proteins
F-Actin Stabilizing proteins
F-Actin De-stabilizing proteins
F-Actin Severing proteins
F-Actin Capping proteins
F-Actin Cross-linking proteins
See Panel 16-3
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A zoo of Actin Binding
Proteins
DO NOT MEMORIZE THIS
TABLE!
Alberts Panel 16-3
Monomer Binding
Proteins
Profilin
stimulates
polymerization in
vivo
Thymosin
inhibits
polymerization
OLD Alberts 16-30
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Monomer Binding Proteins
Profilin promotes polymerization of actin filaments by
binding to G-Actin and stimulating the exchange of ADP for
ATP. This induces the G-Actin protein to have high affinity
for the Plus end of the actin filament.
We also saw how the nucleating factor Formin has binding
sites for Profilin in its “whiskers” domains. Thus, Formin
uses many Profilin molecules to bring G-actin monomers
near the growing Plus end.
The protein Thymosin (don’t have to memorize its name) is
also a G-Actin binding protein but it inhibits actin polymerization
by sequestering the actin monomers. Thus, Thymosin reduces
the concentration of available G-Actin.
OLD Alberts 16-30
Cofilin promotes actin filament depolymerization
Arp2/3 activation factors
Arp2/3 activation factors
Cell 112:453 (2003)
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Cofilin promotes actin filament depolymerization
The protein Cofilin (don’t have to memorize its name)
promotes actin filament depolymerization by breaking the
filament into small fragments (severing) and by destabilizing
those fragments to induce rapid depolymerization.
Cofilin binds to Actin filaments that have hydrolyzed their ATP.
Thus, cofilin will cause the rapid depolymerization of “old”
actin networks but not “new” networks that have just formed
and still contain ATP.
The figure shown here summarizes all the proteins that are
involved in the constant polymerization of actin networks at
the front of a moving cell.
Watch video about Profilin vs Cofilin activity on Canvas or
https://youtu.be/VVgXDW_8O4U
Tropomyosin binds along the length of F-Actin filaments
to stabilize them
It is also used (together with the Troponin Complex) to
regulate the interaction of F-actin and Myosin II in the
muscle sarcomere.
Alberts 16-78
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Actin-Capping Proteins Bind to one end or another of the Actin filament and
prevent both Growth and Disassembly from the Capped End
(+) end: Gelsolin, CapZ (in muscle, don’t memorize name)
(-) end: ARP2/3, Tropomodulin (in muscle, don’t memorize name)
Alberts 16-43
Gelsolin is both a Severing and Capping protein
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Gelsolin is both a Severing and Capping protein
When activated, Gelsolin binds to the side of an actin
filament and severs it.
Gelsolin remains bound and caps the New Plus end of the
actin filament.
In this way it has created two free Minus ends but only one
free Plus end.
In a different set of conditions Gelsolin is inactivated and it
releases the actin filament.
Actin Crosslinking Proteins
These are different examples of Actin Crosslinking Proteins
(You do not have to memorize their names)
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Actin Crosslinking Proteins
F-Actin crosslinking proteins are able to bind to TWO
different actin filaments to link them together.
To do so these proteins must have two actin-binding
domains.
Different cross linking proteins arrange those two
domains in different ways to obtain different types of
networks.
For example, Fimbrin has its two actin-binding domains
side by side in a single polypeptide. Fimbrin is used to
make very tight actin bundles.
Some examples of how these different actin cross
linking proteins are used in the cell are illustrated in the
following slides. You do not have to memorize their
names, just understand the concept and their use.
The actin crosslinking protein Filamin forms orthogonal
actin networks that behave like Gels
These networks give rigidity to the cortex of a cell
Alberts 16-42
See Alberts 16-43 to see what happens in the absence of Filamin
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Villin and Fimbrin make parallel actin bundles that support thin
projections like filopodia and microvilli.
Alberts 16-41
Actin Crosslinking Proteins
Alberts 16-40
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