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= CAMSAP 2 = Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) is a protein that in humans that is involved in microtubule nucleation. This protein acts as a microtubule minus-end anchor and binds microtubules through its CKK domain. CAMSAP2 serves as a strong nucleator for microtubule formation by significantly reducing the nucleation barrier. This protein is an important component in the non-centrosomal, γ-tubulin independent nucleation process.

Microtubules
Microtubules are utilized for three major activities within a cell including cell locomotion, the intracellular transport of organelles, and chromosomal separation during mitosis. Microtubules are made of a globular protein known as tubulin. A tubulin dimer is composed of three forms of tubulin including α-tubulin, β-tubulin and γ-tubulin. α-tubulin is exposed at what is known as the minus-end of microtubules while β-tubulin is exposed at the plus-end. Microtubules are primarily found at the centrosome of cells, however, certain cell types contain a relatively large amount of microtubules that are not located at the centrosome. In particular, neurons, epithelial cells, and muscle cells contain arrays of non-centrosomal microtubules. These non-centrosomal microtubules can arise from the release from former centrosome connectivity, cytoplasmic assembly or the stabilization of non-centrosomal organization sites. Free microtubules in a cell need to be organized and anchored.

Microtubules grow through the polymerization of tubulin. The initial step in this polymerization is a process known as nucleation. γ-tubulin caps help to stabilize minus end microtubules in centrosome bound microtubules and lower the large energy barrier that hinders nucleation. Non-centrosomal microtubules lack γ-tubulin caps and thus lack the benefit of the nucleation activation barrier lowering that γ-tubulin provides for centrosome bound microtubules. CAMSAP 2 provides the function of γ-tubulin for non-centrosomal microtubules.

Function
CAMSAP2 acts as a strong nucleator for non-centrosomal microtubules by lowering the energy barrier needed for polymerization of microtubules at the minus-end without relying on the γ-TuRC template. . Promotion of the microtubule formation is done so by lowering the critical concentration of tubulin needed for microtubule polymerization.

CAMSAP2 plays a role in the chromosomal separation activity of microtubules. During the formation of microtubules, CAMSAP2 continually binds to them which stabilizes them and allows to grow to maturity. Promotion of the microtubule formation is done so by lowering the critical concentration of tubulin needed for microtubule polymerization.

Lowering of Nucleation Energy
CAMSAP2 acts to lower the nucleation energy by lowering the critical concentration of tubulin needed for microtubule polymerization. Polymerization of tubulin into microtubules is done through a process referred to as treadmilling. The regulation of treadmilling is done through the presence of critical concentrations. Critical concentration can be defined as the minimal concentration of total subunits (e.g., tubulin dimers) necessary for polymer assembly. The formula of critical concentration (Cc) is: Cc= Rate of Dissociation/ Rate of Association. CAMSAP2 lowers the critical tubulin concentration needed for polymerization which thus indicates a lower energy barrier of polymerization which thus enhances nucleation of tubulin into microtubules. It is suggested that CAMSAP2 acts as a nucleator by stabilize polymerization intermediates.

Stabilization of Nucleation Intermediates
CAMSAP 2 has been found to form stretches of microtubule lattice which allows the microtubule to resist depolymerization and leads to the stability of the non-centrosomal microtubules. Studies suggest that this protein induces longitudinal growth of tubulin to form a protofilament ring. The protofilaments are present inside condensed nucleation centres, which function as nucleation centres for microtubule polymerization. Cam2-asters are then formed from the growth of these condensed nucleation centres. Microtubules that form from the neighboring asters then come together to form a network.

These Cam2-asters are analogous to the asters formed in centrosomal microtubules, however, the behavior within the asters is very different. Within these asters, CAMSAP2 localizes within the inside of the rings which leads to the assumption that CAMSAP2 aids in stabilizing these intermediates.

CAMSAP-Katanin Complex
While CAMSAP2 works to form networks of microtubule lattice, ATPase Katanin interacts with the protein in order to limit the length of CAMSAP-decorated microtubule stretches. Katanin is a microtubule severing and depolymerization protein. The formation of this complex regulates the effects of CAMSAP proteins on the non-centrosomal microtubules.. Katanin contains p60 and p80 subunits which bind to a region between amino acids 477 and 574 in the N-terminal part of the molecule.

Development
The CAMSAP2 protein is derived from the CAMSAP 2 gene. There are three known isoforms of the protein including X1, X2, and X3.

Structure
The structure of CAMSAP2 is not fully discovered. Proteins within the CAMSAP family are known to have a C-terminal CKK domain which acts to recognize the minus ends of free microtubules. The N-terminal of these proteins contains a calponin homology domain which has an unknown function. The protein also contains several coiled-coils and it is predicted that the first coiled-coil is responsible with interacting with katanin.

Location
CAMSAP2 is found within the cytosol, golgi apparatus and microtubules. . This protein acts on non-centrosomal microtubules specifically. It is discovered to be present in a wide variety of eukaryotic organisms including vertebrates, invertebrates, plants, and fungi. It is present in mammals including humans.

Clinical Applications
Diseases associated with the CAMSAP2 gene include Juvenile myoclonic epilepsy and Benign Epilepsy With Centrotemporal Spikes.

The protein has also been found to be associated with enhancing the cell migration of some cancer cells. CAMSAP2 has bene found to act as an oncogene in hepatocellular carcinoma It plays a role in colorectal cancer cell migration, invasion and metastasis via activation of JNK/c-Jun/MMP-1 signaling pathway.