MALL, a membrane-tetra-spanning proteolipid overexpressed in cancer, is present in membraneless nuclear biomolecular condensates
EntityUAM. Departamento de Biología Molecular
10.1007/s00018-022-04270-wCellular and Molecular Life Sciences 79.5 (2022): 236
ISSN1420-682X (print); 1420-9071 (online)
ProjectGobierno de España. PGC2018-095643-B-I00; Comunidad de Madrid. B2017/BMD-3817/TOMOXLIVER-CM
SubjectsAneuploidy; Biomolecular Condensate; Cytokinesis; Cell Nucleus; Neoplasm; Biología y Biomedicina / Biología
Rights© The Author(s) 2022
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Proteolipids are proteins with unusual lipid-like properties. It has long been established that PLP and plasmolipin, which are two unrelated membrane-tetra-spanning myelin proteolipids, can be converted in vitro into a water-soluble form with a distinct conformation, raising the question of whether these, or other similar proteolipids, can adopt two different conformations in the cell to adapt their structure to distinct environments. Here, we show that MALL, another proteolipid with a membrane-tetra-spanning structure, distributes in membranes outside the nucleus and, within the nucleus, in membrane-less, liquid-like PML body biomolecular condensates. Detection of MALL in one or other environment was strictly dependent on the method of cell fixation used, suggesting that MALL adopts different conformations depending on its physical environment —lipidic or aqueous— in the cell. The acquisition of the condensate-compatible conformation requires PML expression. Excess MALL perturbed the distribution of the inner nuclear membrane proteins emerin and LAP2β, and that of the DNA-binding protein BAF, leading to the formation of aberrant nuclei. This effect, which is consistent with studies identifying overexpressed MALL as an unfavorable prognostic factor in cancer, could contribute to cell malignancy. Our study establishes a link between proteolipids, membranes and biomolecular condensates, with potential biomedical implications
Google Scholar:Rubio-Ramos, Armando - Bernabé-Rubio, Miguel - Labat de Hoz, Leticia - Casares-Arias, Javier - Kremer, Leonor - Alonso, Miguel Angel - Correas Hornero, María Isabel - Alonso Lebrero, Miguel Angel
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Casares-Arias, Javier; Ujue Gonzalez, María; San Paulo, Alvaro; Ventimiglia, Leandro N.; Sadler, Jessica B.A.; Miguez Gómez, David; Labat-de-Hoz, Leticia; Rubio-Ramos, Armando; Rangel, Laura; Bernabe-Rubio, Miguel; Fernandez-Barrera, Jaime; Correas Hornero, María Isabel; Martın-Serrano, Juan; Alonso, Miguel A.