Katanin

From WikiMD's Wellness Encyclopedia

Katanin is a protein complex that plays a crucial role in the severing of microtubules. It is named after the Japanese sword "katana" due to its ability to cut microtubules into smaller pieces. Katanin is essential for various cellular processes, including cell division, cell migration, and the maintenance of neuronal architecture.

Structure[edit | edit source]

Katanin is composed of two subunits: the p60 subunit, which has ATPase activity and is responsible for severing microtubules, and the p80 subunit, which regulates the activity of the p60 subunit and targets it to specific cellular locations. The p60 subunit belongs to the AAA ATPase family, which is known for its role in remodeling cellular structures.

Function[edit | edit source]

Katanin's primary function is to sever microtubules, which are dynamic structures composed of tubulin proteins. By cutting microtubules, katanin helps to regulate their length and organization within the cell. This activity is crucial during mitosis, where microtubules form the mitotic spindle that segregates chromosomes into daughter cells. Katanin also plays a role in neuronal development by remodeling the microtubule network to facilitate the growth and branching of neurons.

Mechanism[edit | edit source]

Katanin severs microtubules by binding to the microtubule lattice and using the energy from ATP hydrolysis to break the bonds between tubulin subunits. This process creates new microtubule ends, which can then be rapidly depolymerized or stabilized, depending on the cellular context. The activity of katanin is tightly regulated by various factors, including post-translational modifications and interactions with other proteins.

Regulation[edit | edit source]

The activity of katanin is regulated by several mechanisms. The p80 subunit targets katanin to specific cellular locations, such as the centrosome, where it can sever microtubules to facilitate the formation of the mitotic spindle. Additionally, katanin activity can be modulated by phosphorylation and other post-translational modifications, which can either enhance or inhibit its microtubule-severing activity.

Clinical Significance[edit | edit source]

Dysregulation of katanin activity has been implicated in various diseases. For example, mutations in the p80 subunit have been linked to hereditary spastic paraplegia, a neurodegenerative disorder characterized by progressive weakness and spasticity of the lower limbs. Abnormal katanin activity has also been associated with cancer, where it may contribute to the uncontrolled proliferation and migration of cancer cells.

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Contributors: Prab R. Tumpati, MD