Microtubule plus-end tracking protein

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PDB 2z0d EBI

Microtubule plus-end tracking proteins (+TIPs) are a diverse group of proteins that associate with the growing plus-ends of microtubules, playing crucial roles in cell division, intracellular transport, and the regulation of microtubule dynamics. These proteins are characterized by their ability to specifically localize to the dynamic plus-ends of microtubules, where they contribute to the stabilization of microtubules, as well as mediate interactions between microtubules and other cellular structures.

Function

+TIPs are involved in a variety of cellular processes. They regulate microtubule dynamics by promoting growth and shrinkage, stabilizing microtubules, and influencing microtubule interactions with membranes, chromosomes, and actin filaments. This regulation is essential for cell polarity, mitosis, and cell migration, among other processes.

Classification

+TIPs can be classified into several families based on their structure and function. Key families include:

• EB Proteins: End-binding proteins that recognize the growing microtubule ends and can recruit other +TIPs.
• CLIPs: Cytoplasmic linker proteins that connect microtubules to various cellular structures.
• XMAP215/TOG: A family of proteins that directly promote microtubule polymerization.
• CLASPs: Microtubule stabilizers that are involved in the regulation of microtubule dynamics at the cell cortex and the Golgi apparatus.

Mechanism of Action

+TIPs recognize specific structures at the microtubule plus-end, such as the GTP cap, which is a region of GTP-bound tubulin subunits that stabilizes the growing microtubule end. Some +TIPs, like EB proteins, can directly bind to these structures, while others interact with microtubules indirectly through scaffolding proteins or by forming complexes with direct binders.

Role in Disease

Dysregulation of +TIP functions has been implicated in various diseases, including cancer, neurodegenerative diseases, and developmental disorders. For example, alterations in the expression or function of certain +TIPs can lead to abnormal cell division and migration, contributing to tumor growth and metastasis.

Research and Applications

Understanding the mechanisms by which +TIPs regulate microtubule dynamics and their roles in cellular processes has significant implications for the development of therapeutic strategies. For instance, targeting +TIP interactions with microtubules has potential in cancer therapy, where the goal is to disrupt abnormal cell division.

See Also

• Microtubule
• Cell division
• Cell migration
• Cytoskeleton

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