AKNA Protein Plays Role In Regulating Differentiation Of Neural Stem Cells

The protein Akna plays a key role in the behavior of neural stem cells, scientists at Helmholtz Zentrum München and Ludwig Maximilian University of Munich (LMU) have discovered.

Led by Prof. Dr. Magdalena Götz, director of the Institute for Stem Cell Research (ISF) at Helmholtz Zentrum München and Chair of Physiological Genomics of the LMU Biomedical Center, the team wanted to identify the factors that regulate the maintenance or differentiation of neural stem cells. To this end, the scientists isolated neural stem cells, which either self-renew and generate additional neural stem cells or differentiate.

“We found that the Akna protein is present in higher concentrations in stem cells that generate neurons, Our experiments showed that low levels of the Akna protein cause stem cells to remain in the stem cell niche, whereas higher levels stimulate them to detach from the niche, thus promoting differentiation,”

explained ISF researcher German Camargo Ortega, first author of the study together with Dr. Sven Falk.

Akna Surprise

The Akna protein is an AT hook transcription factor. A transcription factor is a protein that binds to DNA and regulates the transcription of one or more genes.

The scientists were surprised to discover the position of the protein – namely at the centrosome, an organelle in the cell’s interior that acts as chief architect for the organization of the cytoskeleton and regulates cell division.

“We discovered that an incorrect sequence was originally published for this protein,” Sven Falk reported. “However, our work clearly showed that Akna is located directly at the centrosome.”

The researchers were able to show that Akna recruits and anchors microtubules at the centrosome. This weakens the connections to neighboring cells, and promotes detachment and migration from the stem cell niche.

“Our experiments show that this function also plays an important role in a process known as epithelial-to-mesenchymal transition, or EMT for short”,

explained the study leader Magdalena Götz.

Akna regulates migration of cells into and out of the amplification zone, where many green cells are visible in the picture.  CREDIT Source: Helmholtz Zentrum München

Akna regulates migration of cells into and out of the amplification zone, where many green cells are visible in the picture.
Credit: Helmholtz Zentrum München

Epithelial-to-mesenchymal transition (EMT) denotes a transition from epithelial cells (e.g. skin, gland tissues or mucous membranes) into cells with mesenchymal properties. Mesenchyma is developing tissue showing a high rate of cell division.

“In this process, cells detach from a cluster, proliferate and begin to migrate. This occurs, for example when stem cells migrate to form new neurons, but it can also be harmful in disease, for example when cancer cells leave a tumor to form metastases elsewhere in the body. The novel mechanism that we identified by studying the function of Akna therefore appears to play a key role in a broad range of medically relevant processes,”

Götz said. In the next step, the research team plans to investigate the role of Akna in other stem cells and in the immune system.

Germán Camargo Ortega, Sven Falk, Pia A. Johansson, Elise Peyre, Loïc Broix, Sanjeeb Kumar Sahu, William Hirst, Thomas Schlichthaerle, Camino De Juan Romero, Kalina Draganova, Stanislav Vinopal, Kaviya Chinnappa, Anna Gavranovic, Tugay Karakaya, Thomas Steininger, Juliane Merl-Pham, Regina Feederle, Wei Shao, Song-Hai Shi, Stefanie M. Hauck, Ralf Jungmann, Frank Bradke, Victor Borrell, Arie Geerlof, Simone Reber, Vijay K. Tiwari, Wieland B. Huttner, Michaela Wilsch-Bräuninger, Laurent Nguyen & Magdalena Götz
The centrosome protein AKNA regulates neurogenesis via microtubule organization
Nature (2019) doi – https://doi.org/10.1038/s41586-019-0962-4

Top Image: Helmholtz Zentrum München