Investigating the role of the endoplasmic reticulum (ER)-resident E3 ligase RNF26 in endosomal regulation during mitosis

Eukaryotic cells have evolved complex sub-compartments to partition the cell interior into tiny contained 3D microenvironments. The endoplasmic reticulum (ER) communicates with and regulates other intracellular structures, including the endolysosomal system, through membrane contact sites (MCSs). Dysfunction in endolysosomal spatial-temporal regulation is implicated in neurodegeneration, cancer, and metabolic disease. Recently, it was found that the loss of the ER-associated protein RNF26 disrupts the organization of the endolysosomal system. During mitosis – the self-replication of a cell into two nearly identical daughter cells – the ER and the endolysosomal system are remodeled. The specific role of ER:endosome MCSs and MCS-associated proteins during mitosis is yet to be determined. In this project, we will perform experiments to further understand the role of RNF26 and its regulation during mitosis. We will (1) visualize ER:endosome contact sites during cell division using a fluorescently-tagged cell line and confocal microscopy. We will (2) study the function of RNF26 during mitosis by depletion and overexpression experiments. Candidates will be validated and used to build a model explaining how RNF26 at ER:endosome contacts affect cell division.

Faculty Supervisor:

Samantha Gruenheid

Student:

Partner:

Leiden University Medical Centre

Discipline:

Life Sciences

Sector:

Education

University:

McGill University

Program: