Illustration of cell division with PLK-1 and nucleoporins interacting.

The Key to Cell Division? How PLK-1 and Channel Nucleoporins Team Up to Break Down the Nuclear Envelope

Theo Raines in Science & Nature September 2025 • 4 min read.

"Scientists uncover the essential partnership between PLK-1 and channel nucleoporins in orchestrating nuclear envelope breakdown, a critical step in cell division, opening new avenues for understanding and potentially manipulating cellular processes."

Cell division is a fundamental process of life, essential for growth, repair, and reproduction. In animal cells, this process requires the accurate segregation of chromosomes, which are housed within the nucleus, a compartment bounded by a nuclear envelope. For chromosomes to be properly distributed to daughter cells, the nuclear envelope must break down in a carefully orchestrated event known as nuclear envelope breakdown (NEBD).

While mitotic kinases, a type of enzyme, are known to be involved in NEBD, the precise mechanisms governing their activity and coordination remain unclear. How these kinases work together to initiate and execute this critical event has been a long-standing question in cell biology.

Now, a groundbreaking study published in Developmental Cell sheds light on this intricate process, revealing a key partnership between a specific kinase, Polo-like kinase 1 (PLK-1), and channel nucleoporins, proteins that reside within the nuclear pore complexes. This discovery not only deepens our understanding of NEBD but also highlights the unanticipated role of nucleoporins in regulating this critical step in cell division.

Unlocking the Code: PLK-1's Recruitment and the Role of Channel Nucleoporins

Illustration of cell division with PLK-1 and nucleoporins interacting.

The research team's investigation, spearheaded by Lisa Martino and Lionel Pintard, focused on understanding how PLK-1 contributes to NEBD. Their work revealed that PLK-1, a master regulator of mitosis, is strategically recruited to the nuclear pore complexes just before NEBD. This recruitment, they found, depends on PLK-1's Polo-box domain (PBD), a specialized region that recognizes and binds to specific phosphorylated motifs.

Intriguingly, this recruitment process occurs both in human cells and in Caenorhabditis elegans, a simple nematode worm often used as a model organism in biological research. This evolutionary conservation suggests that this mechanism is fundamental to cell division across species.

PLK-1's Strategic Positioning: PLK-1 localizes to the nuclear pore complexes (NPC) through its Polo-box domain (PBD) in both human cells and C. elegans embryos, ensuring its proximity to key targets.
Channel Nucleoporin Regulation: Channel nucleoporins play a crucial role in positively regulating PLK-1 function during NEBD in C. elegans, highlighting their active involvement in this process.
The NPP-1•NPP-4•NPP-11 Complex: The NPP-1•NPP-4•NPP-11 complex, located within the central channel of the NPC, is responsible for recruiting PLK-1 to the nuclear pore complex, acting as a key anchor.
Direct Binding Mechanism: PLK-1 directly binds to NPP-1, NPP-4, and NPP-11 in a phosphorylation-dependent manner, where phosphorylation acts as a switch that controls the interaction.

The team identified specific channel nucleoporins—NPP-1/Nup58, NPP-4/Nup54, and NPP-11/Nup62—as the crucial factors responsible for anchoring PLK-1 to the nuclear envelope in C. elegans. These nucleoporins, they discovered, are primed at multiple Polo-docking sites by Cdk1, another key mitotic kinase, and by PLK-1 itself. This phosphorylation creates docking sites for PLK-1's PBD, facilitating its binding and subsequent localization to the nuclear envelope.

A New Chapter in Cell Division Research

This research not only provides a detailed understanding of how PLK-1 is recruited to the nuclear envelope but also unveils the surprising role of nucleoporins in regulating this key event in cell division. By acting as docking sites for PLK-1, these nucleoporins facilitate the phosphorylation of downstream targets, ultimately leading to efficient NEBD. These findings open up new avenues for further research, potentially leading to the development of novel therapeutic interventions targeting cell division processes.

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: 10.1016/j.devcel.2017.09.019, Alternate LINK

Title: Channel Nucleoporins Recruit Plk-1 To Nuclear Pore Complexes To Direct Nuclear Envelope Breakdown In C. Elegans

Subject: Developmental Biology

Journal: Developmental Cell

Publisher: Elsevier BV

Authors: Lisa Martino, Stéphanie Morchoisne-Bolhy, Dhanya K. Cheerambathur, Lucie Van Hove, Julien Dumont, Nicolas Joly, Arshad Desai, Valérie Doye, Lionel Pintard

Published: 2017-10-01

Everything You Need To Know

What is the primary function of PLK-1 in cell division?

PLK-1, a Polo-like kinase 1, plays a crucial role in nuclear envelope breakdown (NEBD), a critical step in cell division. It is a master regulator of mitosis. PLK-1 is strategically recruited to the nuclear pore complexes (NPC) just before NEBD, which is essential for the proper segregation of chromosomes during cell division. Its function is facilitated by the Polo-box domain (PBD) which recognizes and binds to specific phosphorylated motifs on channel nucleoporins.

How do channel nucleoporins contribute to the process of nuclear envelope breakdown?

Channel nucleoporins are critical components in the process of nuclear envelope breakdown (NEBD). They act as docking sites for PLK-1, facilitating its localization to the nuclear envelope. Specifically, the NPP-1•NPP-4•NPP-11 complex, located within the central channel of the NPC, recruits PLK-1 to the nuclear pore complex. These nucleoporins are primed by Cdk1 and PLK-1 itself, and the resulting phosphorylation creates docking sites for PLK-1's PBD. This interaction enables the phosphorylation of downstream targets, ultimately leading to efficient NEBD.

What is the role of the NPP-1•NPP-4•NPP-11 complex in the context of PLK-1 recruitment and NEBD?

The NPP-1•NPP-4•NPP-11 complex is a key player in recruiting PLK-1 to the nuclear pore complex (NPC). This complex, located within the central channel of the NPC, functions as a critical anchor for PLK-1. PLK-1 directly binds to NPP-1, NPP-4, and NPP-11. This binding is phosphorylation-dependent, where phosphorylation serves as a switch, controlling the interaction between PLK-1 and the nucleoporins. This recruitment is a prerequisite for the NEBD process, ensuring PLK-1's presence at the right place and time to initiate and regulate the breakdown of the nuclear envelope.

How does the Polo-box domain (PBD) of PLK-1 contribute to the process of nuclear envelope breakdown, and what is its significance?

The Polo-box domain (PBD) of PLK-1 is a specialized region that recognizes and binds to specific phosphorylated motifs on channel nucleoporins. The PBD is critical for the recruitment of PLK-1 to the nuclear pore complexes (NPC) just before nuclear envelope breakdown (NEBD). This recruitment is essential for PLK-1 to carry out its role in NEBD. The PBD's function is evolutionary conserved across species, including human cells and C. elegans, highlighting its fundamental importance in cell division. By binding to these docking sites on channel nucleoporins, the PBD ensures PLK-1's strategic positioning, enabling it to phosphorylate downstream targets and facilitate efficient NEBD.

What are the potential implications of understanding the partnership between PLK-1 and channel nucleoporins for future therapeutic interventions?

Understanding the partnership between PLK-1 and channel nucleoporins opens new avenues for future therapeutic interventions. Because PLK-1 and channel nucleoporins are crucial for cell division, which is a process often dysregulated in diseases like cancer, targeting these components could potentially disrupt uncontrolled cell growth. Specifically, the knowledge of how PLK-1 is recruited and regulated by channel nucleoporins could lead to the development of drugs that interfere with this interaction, ultimately inhibiting cell division in cancer cells. This could involve targeting the Polo-box domain (PBD), the specific phosphorylation sites, or the nucleoporin complex, offering new strategies for cancer treatment and other diseases related to cell division dysregulation.