Triple A patient cells suffering from mitotic defects fail to localize PGRMC1 to mitotic kinetochore fibers

BioRxiv : the Preprint Server for Biology
Ramona JühlenKatrin Köhler

Abstract

Membrane-associated progesterone receptors are restricted to the endoplasmic reticulum and are shown to regulate the activity of cytochrome P450 enzymes which are involved in steroidogenesis or drug detoxification. PGRMC1 and PGRMC2 belong to this group of microsomal receptors and are of interest due to their suspected role during cell cycle. PGRMC1 and PGRMC2 are thought to bind to each other thereby suppressing entry into mitosis. We could previously report that PGRMC2 interacts with the nucleoporin ALADIN which when mutated results in the autosomal recessive disorder triple A syndrome. ALADIN is a novel regulator of mitotic controller Aurora kinase A and depletion of this nucleoporin leads to microtubule instability. In the current study, we present that proliferation is decreased when ALADIN, PGRMC1 or PGRMC2 are over-expressed. Furthermore, we find that depletion of ALADIN results in mis-localization of Aurora kinase A and PGRMC1 in metaphase cells. Additionally, PGRMC2 is over-expressed in triple A patient fibroblasts. Our results emphasize the possibility that loss of the regulatory interaction between ALADIN and PGRMC2 gives rise to a depletion of PGRMC1 at kinetochore fibers and to mitotic errors. This observation may ...Continue Reading

Related Concepts

Establishment and Maintenance of Localization
Study
Glucocorticoid Deficiency With Achalasia
AAAS gene
Specimen Type - Fibroblasts
Enzymes, antithrombotic
Cytochrome P450
Mitotic Metaphase
Metabolic Detoxication, Drug
Metaphase

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