DYNAMIC REGULATION OF CYTOSKELETAL FILAMENTS
For the cytoskeleton to be of most value, the cell needs to be able to regulate nucleation, growth, stability and number. This
is the focus of today’s lecture, with emphasis on actin filaments.
HOW IS THE CYTOSKELETON REGULATED?
In a test tube, there are 3 phases of actin filament concentration: nucleation (lag phase), elongation and stability (equilibrium
phase). In a cell, filaments are much more dynamic – the cell regulates these phases. Direct covalent modification of the
filament subunits regulates some filament properties, but most of the regulation is performed by a large array of accessory
proteins…
ACCESSORY PROTEINS – hundreds of
these control number, length, stability
and orientation of the cytoskeleton.
Proteins that bind to actin and
microtubule filaments or their free
subunits in different ways and with
varying purposes.
Important accessory proteins associated
with microtubules and actin filaments:
NUCLEATION:
REGULATION OF POLYMER
NUMBER
In terms of nucleating
filaments in the cell, getting
to the stable trimer point is
the key goal. In actin dimers,
disaggregation is more
, favoured, and formation of the trimer is relatively rare. To overcome this lag phase, nucleation of the 3 actin monomers is
required. Cell uses proteins to stabilise the initial phase…
NUCLEATION OF ACTIN FILAMENTS
Nucleation of actin occurs mainly in the cell cortex (layer just beneath the plasma membrane) – at or near the plasma
membrane, where most of the actin in the cell is concentrated.
External signals frequently regulate the nucleation of actin filaments at the plasma membrane, allowing the cell to change its
shape and stiffness rapidly in response to changes in its external environment. Internal signals also regulate nucleation.
This nucleation can be catalysed by two different types of protein families:
i) the ARP complex
ii) the forminins.
A) NUMBER: ARPs (ACTN RELATED PROTEINS) NUCLEATE ACTIN FILAMENT GROWTH
Arp 2/3 complex: complex of proteins that includes two actin-related proteins (Arp2 and Arp3), each of which is about 45%
identical to actin (highly structurally related proteins), which are associated with further (approx. 7) accessory proteins. This
is effectively a stabilised dimer.
For the cytoskeleton to be of most value, the cell needs to be able to regulate nucleation, growth, stability and number. This
is the focus of today’s lecture, with emphasis on actin filaments.
HOW IS THE CYTOSKELETON REGULATED?
In a test tube, there are 3 phases of actin filament concentration: nucleation (lag phase), elongation and stability (equilibrium
phase). In a cell, filaments are much more dynamic – the cell regulates these phases. Direct covalent modification of the
filament subunits regulates some filament properties, but most of the regulation is performed by a large array of accessory
proteins…
ACCESSORY PROTEINS – hundreds of
these control number, length, stability
and orientation of the cytoskeleton.
Proteins that bind to actin and
microtubule filaments or their free
subunits in different ways and with
varying purposes.
Important accessory proteins associated
with microtubules and actin filaments:
NUCLEATION:
REGULATION OF POLYMER
NUMBER
In terms of nucleating
filaments in the cell, getting
to the stable trimer point is
the key goal. In actin dimers,
disaggregation is more
, favoured, and formation of the trimer is relatively rare. To overcome this lag phase, nucleation of the 3 actin monomers is
required. Cell uses proteins to stabilise the initial phase…
NUCLEATION OF ACTIN FILAMENTS
Nucleation of actin occurs mainly in the cell cortex (layer just beneath the plasma membrane) – at or near the plasma
membrane, where most of the actin in the cell is concentrated.
External signals frequently regulate the nucleation of actin filaments at the plasma membrane, allowing the cell to change its
shape and stiffness rapidly in response to changes in its external environment. Internal signals also regulate nucleation.
This nucleation can be catalysed by two different types of protein families:
i) the ARP complex
ii) the forminins.
A) NUMBER: ARPs (ACTN RELATED PROTEINS) NUCLEATE ACTIN FILAMENT GROWTH
Arp 2/3 complex: complex of proteins that includes two actin-related proteins (Arp2 and Arp3), each of which is about 45%
identical to actin (highly structurally related proteins), which are associated with further (approx. 7) accessory proteins. This
is effectively a stabilised dimer.
