The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation

Christina B Wölwer; Nathan Gödde; Luke B Pase; Imogen A Elsum; Krystle Y B Lim; Faruk Sacirbegovic; Carl R Walkley; Sarah Ellis; Shigeo Ohno; Fumio Matsuzaki; Sarah M Russell; Patrick O Humbert

doi:10.1371/journal.pone.0170295

The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation

PLoS One. 2017 Jan 17;12(1):e0170295. doi: 10.1371/journal.pone.0170295. eCollection 2017.

Authors

Christina B Wölwer^{1

2}, Nathan Gödde^{1

2}, Luke B Pase¹, Imogen A Elsum¹, Krystle Y B Lim², Faruk Sacirbegovic^{3

4}, Carl R Walkley^{5

6}, Sarah Ellis^{3

4}, Shigeo Ohno⁷, Fumio Matsuzaki⁸, Sarah M Russell^{4

9

10}, Patrick O Humbert^{1

2

4

9

11}

Affiliations

¹ Cell Cycle and Cancer Genetics, Peter MacCallum Cancer Centre, East Melbourne, Australia.
² La Trobe Institute for Molecular Science, Department of Biochemistry and Genetics, La Trobe University, Melbourne, Australia.
³ Immune Signaling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.
⁴ Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
⁵ St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
⁶ Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria.
⁷ Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan.
⁸ Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe, Japan.
⁹ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
¹⁰ Centre for Micro-Photonics, Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Hawthorn, Australia.
¹¹ Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.

Abstract

Erythroid enucleation is the process by which the future red blood cell disposes of its nucleus prior to entering the blood stream. This key event during red blood cell development has been likened to an asymmetric cell division (ACD), by which the enucleating erythroblast divides into two very different daughter cells of alternate molecular composition, a nucleated cell that will be removed by associated macrophages, and the reticulocyte that will mature to the definitive erythrocyte. Here we investigated gene expression of members of the Par, Scribble and Pins/Gpsm2 asymmetric cell division complexes in erythroid cells, and functionally tested their role in erythroid enucleation in vivo and ex vivo. Despite their roles in regulating ACD in other contexts, we found that these polarity regulators are not essential for erythroid enucleation, nor for erythroid development in vivo. Together our results put into question a role for cell polarity and asymmetric cell division in erythroid enucleation.

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Asymmetric Cell Division / physiology*
Carrier Proteins / physiology*
Cell Adhesion Molecules / physiology*
Cell Cycle Proteins
Cell Differentiation*
Cell Nucleus / metabolism
Cell Polarity
Cells, Cultured
Erythroblasts / cytology*
Erythroblasts / metabolism
Erythropoiesis / physiology*
Female
Intracellular Signaling Peptides and Proteins / physiology*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
Cell Adhesion Molecules
Cell Cycle Proteins
Intracellular Signaling Peptides and Proteins
LGN protein, mouse
Pard3 protein, mouse
scribble protein, mouse

Grants and funding

The studies presented here were supported by the Peter MacCallum Cancer Foundation and a grant from the National Health and Medical Research Council of Australia (NHMRC). CBW was supported by the Australian Postgraduate Award (APA). POH and SMR were supported by a Senior Research Fellowship from the NHMRC.