Unveiling the Intricate Dance of Cells: New Findings on Nuclear Repositioning

November 30, 2023

Prof Jörg Renkawitz, Janina Kroll and their team were able to demonstrate how fast migrating cells employ nuclear repositioning to flexibly navigate in microenvironments.

The ability of cells to navigate their path while moving themselves forward is critical for innate and adaptive immune responses, organismal development, tissue maintenance, and single-cell organisms.
Professor Jörg Renkawitz and his team explore the phenomenon of nuclear repositioning as a key mechanism that enables cells to flexibly adapt the direction of their path to diverse environmental guidance cues.

Motile cells face diverse guidance cues at the same time, raising the question of how they respond to multiple and potentially competing signals on their paths. In this study, the team, led by PhD student Janina Kroll, was able to reveal that very fast migrating cells, called amoeboid cells, require nuclear repositioning for adaptive pathfinding in microenvironments that are composed of various guidance cues. This nuclear repositioning, also called nucleokinesis, acts like an internal GPS for amoeboid cells, meaning that motile amoeboid cells precisely detect the internal localization of their nucleus inside their cell body. This accurate detection enables motile cells to constantly align the internal movement of the nucleus with the movement of the entire cell body. The research team of Renkawitz established that nucleokinesis is required for amoeboid cell navigation. Given that many immune cells, amoebae, and some cancer cells utilize an amoeboid migration strategy, these results suggest that nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease.

Using models such as immune cells including dendritic cells and T cells, alongside the amoeba Dictyostelium discoideum, the research team showed the intricate ways in which cells adapt and navigate within complex microenvironments. The study provides a fascinating glimpse into the cellular world, showcasing the dynamic interplay between cells and their surroundings.

One of the highlights is a movie that captures a dendritic cell skillfully maneuvering through a pillar maze. In the movie, the nucleus is highlighted in cyan, while the myosin motor protein is vividly depicted in a fire color-coding scheme. This visualization offers a unique perspective on the cellular processes at play during navigation, demonstrating the remarkable flexibility and adaptability of these cells.

The findings, published in the journal EMBO, open a new way for further exploration of the underlying mechanisms of cell migration and navigation, with potential implications for fields such as immunology and cell biology. Professor Renkawitz explains, "The ability to adapt to competing mechanochemical guidance cues through nuclear repositioning is a fascinating aspect of cellular behavior, with implications for various fields of research."

This groundbreaking research not only expands our understanding of cell migration but also holds promise for the development of innovative approaches in fields ranging from immunology, developmental biology and tumor biology.

Publication:
Adaptive pathfinding by nucleokinesis during amoeboid migration, Kroll et al, EMBO J 2023