Kinesin-13 motor protein interacting with a microtubule

Unlocking the Secrets of Kinesin-13: How These Tiny Motors Shape Our Cells

Rhea Morgan in Science & Nature August 2025 • 4 min read.

"Dive into the world of microtubule depolymerizing kinesins and discover how their unique structures and functions are critical for cell division, neuronal development, and more."

The Kinesin superfamily is a large group of molecular motors that use ATP to regulate their interaction with the microtubule cytoskeleton. These motors perform various cellular functions, including the specialist Kinesin-13 family, which depolymerizes microtubules.

Members of the Kinesin-13 family use their microtubule-destabilizing activity to regulate processes such as chromosome segregation, maintenance of cilia, and neuronal development. Understanding the structure and function of these kinesins is crucial for comprehending their role in cell dynamics.

This article explores the current understanding of the structure of the Kinesin-13 family and the roles different parts of these proteins play in their microtubule depolymerization activity and broader functions.

What Makes Kinesin-13s Specialist Microtubule Depolymerisers?

Kinesin-13 motor protein interacting with a microtubule

Kinesin-13s, characterized by a conserved motor domain, use ATP turnover to regulate interaction with the microtubule cytoskeleton. Unlike most kinesins, Kinesin-13s don't support microtubule motility; instead, they diffuse on microtubules and depolymerize them from both ends. The genome of most eukaryotes has at least one Kinesin-13, with members suggested as major regulators of microtubule length. Yeast typically lacks a Kinesin-13, with a Kinesin-8 family member fulfilling the role of microtubule length regulation.

These kinesins play key roles in regulating microtubule length and are particularly important during meiosis and mitosis in higher eukaryotes. First identified in mammals, KIF2A and MCAK, along with the Xenopus homologue XKCM1, alter microtubule dynamics. Depletion of XKCM1 leads to long microtubules, disorganised spindles, and chromosome misalignment. Other Kinesin-13s also show microtubule-destabilizing activity.

KLP10A (Drosophila): Regulates spindle microtubules, centriole length.
KLP-7 (Caenorhabditis elegans): Prevents ectopic cytoplasmic nucleation of microtubules.
MCAK/KIF2C (Mammalian): Centromeric localisation contributes to kinetochore-microtubule attachments and chromosome oscillations.

The most highly studied Kinesin-13 is MCAK/KIF2C. Its centromeric pool contributes to the formation of kinetochore-microtubule attachments and to chromosome oscillations. Aurora B kinase regulates MCAK activity at centromeres. MCAK is also found at growing microtubule tips, tracking them in an EB-dependent manner. KIF18B mediates plus tip targeting of MCAK. KIF2A plays a critical role in neurons to regulate axonal pruning. KIF2B associates with Cep170 to target the spindle. KIF24 regulates the length of cilia and has a longer C-terminal region.

Open Questions and Future Directions

While the Kinesin-13 motor domain has potent microtubule depolymerizing activity, the molecular characteristics that confer this specialist activity are not fully understood. Future research should focus on how the tubulin-binding interface is specifically adapted to recognize the microtubule end and how family-specific sequence motifs contribute to this recognition. Further exploration is also needed to understand the role of the neck region and the long-range intramolecular interactions in regulating Kinesin-13 activity and function.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1042/bst20180350, Alternate LINK

Title: Parts List For A Microtubule Depolymerising Kinesin

Subject: Biochemistry

Journal: Biochemical Society Transactions

Publisher: Portland Press Ltd.

Authors: Claire T. Friel, Julie P. Welburn

Published: 2018-11-22

Everything You Need To Know

What makes Kinesin-13 proteins unique compared to other kinesins?

Unlike most kinesins that facilitate movement along microtubules, Kinesin-13 proteins are specialized microtubule depolymerizers. They utilize ATP to regulate their interaction with the microtubule cytoskeleton but, instead of supporting microtubule motility, they diffuse on microtubules and depolymerize them from both ends, effectively shortening the microtubules. This microtubule-destabilizing activity is crucial for various cellular processes. While the motor domain of Kinesin-13s is responsible for microtubule depolymerization, the precise molecular mechanisms that enable this specialized activity, particularly how they recognize and bind to microtubule ends, are still being researched.

In what cellular processes do Kinesin-13 family members play a significant role?

Kinesin-13 family members are essential in several cellular processes, including chromosome segregation during cell division, the maintenance of cilia, and neuronal development. Specifically, MCAK/KIF2C is involved in kinetochore-microtubule attachments and chromosome oscillations, while KIF2A regulates axonal pruning in neurons. These functions highlight the importance of Kinesin-13s in ensuring proper cell structure and function. Their ability to regulate microtubule length is critical for the successful execution of these cellular events, and disruptions in their function can lead to developmental and functional abnormalities.

Which specific Kinesin-13 proteins have been extensively studied, and what are their known functions?

Several Kinesin-13 proteins have been well-studied, including MCAK/KIF2C (mammalian), KIF2A, and XKCM1 (Xenopus homologue). MCAK/KIF2C is known for its role in forming kinetochore-microtubule attachments and contributing to chromosome oscillations during cell division. KIF2A is crucial in regulating axonal pruning in neurons, impacting neuronal development and function. XKCM1, when depleted, results in elongated microtubules, disorganized spindles, and misaligned chromosomes, highlighting its importance in microtubule dynamics. Additionally, KLP10A in Drosophila regulates spindle microtubules and centriole length, while KLP-7 in Caenorhabditis elegans prevents ectopic cytoplasmic nucleation of microtubules.

How is the activity of MCAK/KIF2C regulated, and why is this regulation important?

The activity of MCAK/KIF2C is regulated by Aurora B kinase at the centromeres. This regulation is critical for its function in kinetochore-microtubule attachments and chromosome oscillations during cell division. Aurora B kinase influences MCAK activity, ensuring that chromosome segregation occurs correctly. Without proper regulation of MCAK/KIF2C, chromosome misalignment and segregation errors can occur, leading to genomic instability and potentially contributing to diseases like cancer. KIF18B also mediates plus tip targeting of MCAK, further highlighting the complex regulatory mechanisms governing its function.

What are some open questions and future research directions regarding Kinesin-13 proteins?

Despite significant advances in understanding Kinesin-13 proteins, several open questions remain. The molecular characteristics that confer their specialized microtubule depolymerizing activity are not fully understood, particularly how the tubulin-binding interface is specifically adapted to recognize the microtubule end. Future research should focus on identifying family-specific sequence motifs that contribute to this recognition. Additionally, the role of the neck region and long-range intramolecular interactions in regulating Kinesin-13 activity and function requires further exploration. A deeper understanding of these aspects could provide insights into the precise mechanisms of microtubule depolymerization and the regulation of cellular processes involving Kinesin-13s.