ALIX in cell division in vivo
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AbstractCell division is a fundamental process supporting life. Uncontrolled cell division can give rise to tumourigenesis. Knowledge about the molecular mechanisms of cell division is therefore crucial for understanding the inner life of the cell, but also for understanding diseases such as cancer. Many aspects of cell division remain to be elucidated, but especially how cell division is regulated in a living, multicellular organism is not well understood. To shed light on this essential process in vivo, Anette Lie-Jensen and colleagues used the fruit fly, Drosophila melanogaster, as a model organism. Lie-Jensen and colleagues showed that the multifunctional scaffold protein ALIX is involved in orienting the mitotic spindle. Correct mitotic spindle orientation is necessary to ensure that cell fate determinants are properly distributed between the two daughter cells, and spindle misorientation can lead to tumourigenesis. In addition, Lie-Jensen and colleagues studied cytokinetic abscission. Cytokinetic abscission is the physical separation of the newly formed daughter cells. ALIX is known to be involved in this process in human cells, and the work done in this thesis showed that ALIX promotes cytokinetic abscission in a multicellular context in Drosophila, and thus that its role in abscission is evolutionarily conserved. Enveloped viruses take advantage of cellular machineries to bud through and abscise from the plasma membrane of the infected cell. ALIX is known to be involved in this process. Lie-Jensen and colleagues discovered that ALIX is recruited to the midbody during cytokinetic abscission in Drosophila via an analogous mechanism as during virus budding in human cells. Taken together, Lie-Jensen and colleagues have identified that ALIX plays an important role in both early and late phases of cell division in vivo. This work has thus shed light on how cells divide in a living organism, knowledge relevant for understanding diseases such as cancer.
List of papers
|Paper I. ALIX and ESCRT-III coordinately control cytokinetic abscission during germline stem cell division in vivo. Eikenes ÅH, Malerød L, Christensen AL, Steen CB, Mathieu J, Nezis IP, Liestøl K, Huynh JR, Stenmark H, Haglund K. PLoS Genet. 2015 Jan 30;11(1). DOI:10.1371/journal.pgen.1004904. The article is included in the thesis. Also available at: https://doi.org/10.1371/journal.pgen.1004904|
|Paper II. Antibody staining in Drosophila germaria. Lie-Jensen A, Haglund K. Methods Mol Biol. 2016;1457:19-33. DOI:10.1007/978-1-4939-3795-0_3. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1007/978-1-4939-3795-0_3|
|Paper III. Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics. Malerød L, Le Borgne R, Lie-Jensen A, Eikenes ÅH, Brech A, Liestøl K, Stenmark H, Haglund K. EMBO J. 2018 Jul 2;37(13). DOI:10.15252/embj.201797741. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.15252/embj.201797741|
|Paper IV. Centralspindlin recruits ALIX to the midbody during cytokinetic abscission in Drosophila via a mechanism analogous to virus budding. Lie-Jensen A, Ivanauskiene K, Malerød L, Jain A, Tan KW, Laerdahl JK, Liestøl K, Stenmark H, Haglund K. Curr Biol. 2019 Oct 21;29(20):3538-3548. DOI:10.1016/j.cub.2019.09.025. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.cub.2019.09.025|