Microtubule-associated protein
Encyclopedia
In cell biology
, microtubule-associated proteins (MAPs) are proteins that interact with the microtubule
s of the cellular cytoskeleton
.
subunits that make up microtubules to regulate their stability. A large variety of MAPs have been identified in many different cell type
s, and they have been found to carry out a wide range of functions. These include both stabilizing and destabilizing microtubules, guiding microtubules towards specific cellular locations, cross-linking microtubules and mediating the interactions of microtubules with other proteins in the cell .
Within the cell, MAPs bind directly to the tubulin dimers of microtubules. This binding can occur with either polymer
ized or depolymerized tubulin, and in most cases leads to the stabilization of microtubule structure, further encouraging polymerization. Usually, it is the C-terminal domain of the MAP that interacts with tubulin, while the N-terminal domain can bind with cellular vesicles, intermediate filament
s or other microtubules. MAP-microtubule binding is regulated through MAP phosphorylation. This is accomplished through the function of the microtubule-affinity-regulating-kinase (MARK) protein. Phosphorylation of the MAP by the MARK causes the MAP to detach from any bound microtubules . This detachment is usually associated with a destabilization of the microtubule causing it to fall apart. In this way the stabilization of microtubules by MAPs is regulated within the cell through phosphorylation.
) and MAP1b (MAP1B
), which make up the MAP1 family, bind to microtubules differently than other MAPs, utilizing charged interactions . While the C-terminals of these MAPs bind the microtubules, the N-terminals bind other parts of the cytoskeleton or the plasma membrane to control spacing of the microtubule within the cell. Members of the MAP1 family are found in the axon
s and dendrite
s of nerve cells .
) and tau (MAPT), which participate in determining the structure of different parts of nerve cells - MAP2 being found mostly in dendrites and tau in the axon. These proteins have a conserved C-terminal
microtubule-binding domain and variable N-terminal
domains projecting outwards probably interacting with other proteins. MAP2 and tau stabilize microtubules, and thus shift the reaction kinetics in favor of addition of new subunits, accelerating microtubule growth. Both MAP2 and tau have been shown to stabilize microtubules by binding to the outer surface of the microtubule protofilaments ,. A single study has been suggested that MAP2 and tau bind on the inner microtubule surface on same site in tubulin monomers as the drug Taxol
which is used in treating cancer . However, the evidence is in favor of MAP2 and tau binding to the outer microtubule surface and this study has not been confirmed. MAP2 binds in a cooperative manner with many MAP2 proteins binding a single microtubule to promote stabilization. Tau as well helps to stabilize microtubules, however it forms the additional, important function of facilitating bundling of microtubules within the nerve cell .
The function of tau has been linked to the neurological condition known as Alzheimer's Disease
. In the nervous tissue of Alzheimer's patients tau forms abnormal aggregates. This aggregated tau is often severely modified, most commonly through hyperphosphorylation. As described above, phosphorylation of MAPs causes them to detach from microtubules. Thus, the hyperphosphorylation of tau leads to massive detachment which in turn greatly reduces the stability of microtubules in nerve cells . This increase in microtubule instability may be one of the main causes of the symptoms of Alzheimer's Disease.
In contrast to the MAPs described above, MAP4 (MAP4
) is not confined to just nerve cells, but rather can be found in nearly all types of cells. Like MAP2 and tau, MAP4 is responsible for stabilization of microtubules . MAP4 has also been linked to the process of cell division .
(the "X" stands for Xenopus
). XMAP215 has generally been linked to microtubule stabilization. During mitosis
the dynamic instability of microtubules has been observed to rise approximately tenfold. This is partly due to phosphorylation of XMAP215, which makes catastrophes (rapid depolymerization of microtubules) more likely . In this way the phosphorylation of MAPs plays a role in mitosis.
There are many other proteins which affect microtubule behavior, such as catastrophin
, which destabilizes microtubules, katanin, which severs them, cytoplasmic linker associated protein
s (CLASPs), which facilitate interaction with the plasma membrane, and a number of motor proteins that transport vesicles along them. Certain motor proteins were originally designated as MAPs before it was found that they utilized ATP hydrolysis to transport cargo. In general, all these proteins are not considered "MAPs" because they do not bind directly to tubulin monomers, a defining characteristic of MAPs . MAPs bind directly to microtubules to stabilize or destabilize them and link them to various cellular components including other microtubules.
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
, microtubule-associated proteins (MAPs) are proteins that interact with the microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s of the cellular cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
.
Function
MAPs bind to the tubulinTubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
subunits that make up microtubules to regulate their stability. A large variety of MAPs have been identified in many different cell type
Cell type
A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...
s, and they have been found to carry out a wide range of functions. These include both stabilizing and destabilizing microtubules, guiding microtubules towards specific cellular locations, cross-linking microtubules and mediating the interactions of microtubules with other proteins in the cell .
Within the cell, MAPs bind directly to the tubulin dimers of microtubules. This binding can occur with either polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
ized or depolymerized tubulin, and in most cases leads to the stabilization of microtubule structure, further encouraging polymerization. Usually, it is the C-terminal domain of the MAP that interacts with tubulin, while the N-terminal domain can bind with cellular vesicles, intermediate filament
Intermediate filament
Intermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin , and that of 25 nm microtubules, although they were initially designated...
s or other microtubules. MAP-microtubule binding is regulated through MAP phosphorylation. This is accomplished through the function of the microtubule-affinity-regulating-kinase (MARK) protein. Phosphorylation of the MAP by the MARK causes the MAP to detach from any bound microtubules . This detachment is usually associated with a destabilization of the microtubule causing it to fall apart. In this way the stabilization of microtubules by MAPs is regulated within the cell through phosphorylation.
Types
The numerous identified MAPs have been largely divided into two categories: Type I including MAP1 proteins and type II including MAP2, MAP4 and tau proteins.Type I: MAP1
MAP1a (MAP1AMAP1A
Microtubule-associated protein 1A is a protein that in humans is encoded by the MAP1A gene.-Further reading:...
) and MAP1b (MAP1B
MAP1B
Microtubule-associated protein 1B is a protein that in humans is encoded by the MAP1B gene.-Interactions:MAP1B has been shown to interact with Acidic leucine-rich nuclear phosphoprotein 32 family member A and RASSF1.-Further reading:...
), which make up the MAP1 family, bind to microtubules differently than other MAPs, utilizing charged interactions . While the C-terminals of these MAPs bind the microtubules, the N-terminals bind other parts of the cytoskeleton or the plasma membrane to control spacing of the microtubule within the cell. Members of the MAP1 family are found in the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s and dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
s of nerve cells .
Type II: MAP2, MAP4 and tau
Also found exclusively in nerve cells are the most well studied MAPs, MAP2 (MAP2MAP2
Microtubule-associated protein 2 is a protein that in humans is encoded by the MAP2 gene.-Interactions:MAP2 has been shown to interact with Grb2, NEFL and MYO7A.. MAP2 is suspected of interacting with tubulin.-Further reading:...
) and tau (MAPT), which participate in determining the structure of different parts of nerve cells - MAP2 being found mostly in dendrites and tau in the axon. These proteins have a conserved C-terminal
C-terminal end
The C-terminus is the end of an amino acid chain , terminated by a free carboxyl group . When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus...
microtubule-binding domain and variable N-terminal
N-terminal end
The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group . The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus...
domains projecting outwards probably interacting with other proteins. MAP2 and tau stabilize microtubules, and thus shift the reaction kinetics in favor of addition of new subunits, accelerating microtubule growth. Both MAP2 and tau have been shown to stabilize microtubules by binding to the outer surface of the microtubule protofilaments ,. A single study has been suggested that MAP2 and tau bind on the inner microtubule surface on same site in tubulin monomers as the drug Taxol
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
which is used in treating cancer . However, the evidence is in favor of MAP2 and tau binding to the outer microtubule surface and this study has not been confirmed. MAP2 binds in a cooperative manner with many MAP2 proteins binding a single microtubule to promote stabilization. Tau as well helps to stabilize microtubules, however it forms the additional, important function of facilitating bundling of microtubules within the nerve cell .
The function of tau has been linked to the neurological condition known as Alzheimer's Disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. In the nervous tissue of Alzheimer's patients tau forms abnormal aggregates. This aggregated tau is often severely modified, most commonly through hyperphosphorylation. As described above, phosphorylation of MAPs causes them to detach from microtubules. Thus, the hyperphosphorylation of tau leads to massive detachment which in turn greatly reduces the stability of microtubules in nerve cells . This increase in microtubule instability may be one of the main causes of the symptoms of Alzheimer's Disease.
In contrast to the MAPs described above, MAP4 (MAP4
MAP4
Microtubule-associated protein 4 is a protein that in humans is encoded by the MAP4 gene.-Further reading:...
) is not confined to just nerve cells, but rather can be found in nearly all types of cells. Like MAP2 and tau, MAP4 is responsible for stabilization of microtubules . MAP4 has also been linked to the process of cell division .
Other MAPs, and naming issues
Another MAP whose function has been investigated during cell division is known as XMAP215CKAP5
Cytoskeleton-associated protein 5 is a microtubule-associated protein that in humans is encoded by the CKAP5 gene. It is the homolog of the Xenopus protein XMAP215 and is also known as ch-Tog....
(the "X" stands for Xenopus
Xenopus
Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus...
). XMAP215 has generally been linked to microtubule stabilization. During mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
the dynamic instability of microtubules has been observed to rise approximately tenfold. This is partly due to phosphorylation of XMAP215, which makes catastrophes (rapid depolymerization of microtubules) more likely . In this way the phosphorylation of MAPs plays a role in mitosis.
There are many other proteins which affect microtubule behavior, such as catastrophin
Catastrophin
Catastrophin, or KIF2, is a microtubal motor protein which causes destabilization, ie. increases dynamic instability, of the microtubule plus end. It is specifically a kinesin-like protein with a motor domain situated in the middle portion of its heavy chain...
, which destabilizes microtubules, katanin, which severs them, cytoplasmic linker associated protein
CLASP1
Cytoplasmic linker associated protein 1, also known as CLASP1 is a protein which in humans is encoded by the CLASP1 gene.- Function :...
s (CLASPs), which facilitate interaction with the plasma membrane, and a number of motor proteins that transport vesicles along them. Certain motor proteins were originally designated as MAPs before it was found that they utilized ATP hydrolysis to transport cargo. In general, all these proteins are not considered "MAPs" because they do not bind directly to tubulin monomers, a defining characteristic of MAPs . MAPs bind directly to microtubules to stabilize or destabilize them and link them to various cellular components including other microtubules.