Microtubule plus-end tracking protein

+TIP-proteins are a type of microtubule associated protein (MAP) which are fundamentally based on the plus-ends of microtubules. +TIP-proteins are arranged in highly diverse groups which are classified based on their structural components; however, all share a same conception in the association with the plus end of microtubules and the ability to maintain interactions between themselves regardless of their differences. +TIP-proteins can be either membrane bounded or cytoplasmic, depending on the certain type of +TIPs. Most +TIP-proteins track the ends of extending microtubules in a non-autonomous manner.

MTB Microtubule Plus End Tracking Protein (+TIP) of Neurospora crassa-pone.

Microtubules plus end tracking mainly with the regulation of microtubule dynamics.

Its certain localization at the microtubule ends makes it a highly relevant aspect in regulation, whether it is promoting growth by catalyzing the specific addition of tubulin to the microtubule ends or by balancing microtubules at the cell cortex, its role in regulation (though still not fully understood in terms of mechanisms) makes +TIP-proteins a main attribute to the overall function of microtubules generally. Another important concept for +TIP-proteins is allocating microtubule addition and dynamical regulation at mitotic kintechores.[1] Also, they contribute in the extension of endoplasmic reticulum tubules together at expanding microtubule ends. Furthermore, +TIP-proteins aid in advocating organization of specialized microtubule array, take for example the discretely arranged bipolar microtubule bundles in fission yeast or mitotic spindles customarily.

Cep169-a-Novel-Microtubule-Plus-End-Tracking-Centrosomal-Protein-Binds-to-CDK5RAP2-and-Regulates-pone.0140968.s002

In addition to the +TIP-proteins basic known functions, the proteins also are crucial for the linkages between microtubule ends and other cellular structure. Take for instance their ability to bind microtubule tips to the cell cortex by colliding to plasma membrane associated proteins or (by some +TIPs) straight forwardly to actin fiber. Moreover, +TIP-protein complexes in budding yeast are utilized for myosin based transport of microtubule ends. Microtubule plus-end trafficking proteins engage in microtubule actin crosstalk, such as the CLIP-170 (+TIP-protein) that controls actin polymerization which is a necessity for the process of phagocytosis done by mammalian cells.[2]

+TIP-proteins have been known for an extravagant accumulation by the centrosomes and other structural organizing centers of cells. This leads to the basic assumption that +TIP-proteins may aid in microtubule nucleation and anchoring; however, its distinct role at centrosomes still awaits evidential findings. Overall, +TIPs play a critical part in morphogenesis, cell division, and motility.

Certain classifications of +TIPs (based on structural domains)

About 20 different families of microtubule plus-end trafficking proteins have been discovered since the first finding of +TIP-protein CLIP-170 (CLIP1) in 1999. Since then +TIPs have been studied thoroughly and still are. The largest group of +TIPs contain complex and large proteins which have low-complexity sequence areas which are affluent in standard proline and serine residues. These type of proteins share a structural basic Ser-x-lle-Pro (x relates to any amino acid). This certain “code” allows these specific complex proteins to be recognizable to another family of +TIPs, known as the EB proteins.The end-binding proteins (EB proteins), have a precise N-terminal domain which is accountable for microtubule binding. The C-terminus however, sustains an alpha-helical coiled region which regulates parallel dimerization of EB monomers and comprises an acidic tail (attaining EEY/F motif) along with an EB homology domain (EBH). The EBH domain and or the EEY/F motif allow the EB proteins to physically interrelate with an array of +TIP in order to recruit them to microtubule ends.[3]

Other classes of +TIPs include the cytoskeleton-associated proteins which are known for their glycine rich domain and a special conserved hydrophobic cavity which permits them to confer interactions with microtubules and EB proteins. There is also, a class of the +TIPs which substantiates a TOG domain, arranged properly these domains allow mediation of binding to tubulin and are important for microtubule growth correlated activity. Basically, the brief classification of +TIPs can be made prior to the specific domain and function rudiments of the particular protein; there exist many more +TIP-proteins but these correspond to the main oriented and highly studied +TIPs.

The-Fission-Yeast-XMAP215-Homolog-Dis1p-Is-Involved-in-Microtubule-Bundle-Organization-pone.0014201.s011
EB Proteins


SxlP proteins
TOG proteins
Motor proteins
Other proteins
PDB 2z0d EBI
Examination-of-actin-and-microtubule-dependent-APC-localisations-in-living-mammalian-cells-1471-2121-7-3-S11
Kebab-Kinetochore-and-EB1-Associated-Basic-Protein-That-Dynamically-Changes-Its-Localisation-during-pone.0024174.s001
TOG-Proteins-Are-Spatially-Regulated-by-Rac-GSK3β-to-Control-Interphase-Microtubule-Dynamics-pone.0138966.s007

Expanding the study of +TIPs

Scientists continue to further their understanding of certain mechanisms done by +TIP-proteins and the range of different types of these proteins. Understandings of microtubule plus-end trafficking proteins has greatly expanded since the discovery of CLAP1, and surely will continue to expand as predicted by many researchers and cytologist. Currently, +TIP-proteins may play critical roles in more than just the general aspects known; also with other particular cell structures along with the known structures which are the endoplasmic reticulm, F-actin, vesicles, microtubules, jintechores, cell cortex, and centrosomes.

See also

References

  1. ↑ Akhmanova, Anna. "Microtubule plus-end-tracking protein".
  2. ↑ Akhmanova, Anna; Steinmetz, Michel. "Microtubules +TIPs at a glance".
  3. ↑ "structures and functions of microtubules".
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