Arginine methylation regulates MEIS2 nuclear localization to promote neuronal differentiation of adult SVZ progenitors

  • Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate.
Metadaten
Author:Jasmine Kolb, Marie Anders-Maurer, Tanja Müller, Ann-Christin Hau, Britta Moyo Grebbin, Wiebke Kallenborn-Gerhardt, Christian Behrends, Dorothea Schulte
URN:urn:nbn:de:hebis:30:3-474723
DOI:https://doi.org/10.1016/j.stemcr.2018.03.010
ISSN:2213-6711
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29641989
Parent Title (English):Stem cell reports
Publisher:Cell Press ; Elsevier
Place of publication:Maryland Heights, MO ; [New York, NY]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/04/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/11/01
Tag:CRM1; MEIS2; PBX1; TALE-homdomain protein; controlled nuclear import; neurogenesis; posttranslational modification; stem cell niche; subventricular zone
Volume:10
Issue:4
Page Number:9
First Page:1184
Last Page:1192
Note:
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
HeBIS-PPN:440895944
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0