Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

Jasmine Kolb, Marie Anders-Maurer, Tanja Müller, Ann Christin Hau, Britta Moyo Grebbin, Wiebke Kallenborn-Gerhardt, Christian Behrends, Dorothea Schulte*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

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. A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.”

Original languageEnglish
Pages (from-to)1184-1192
Number of pages9
JournalStem Cell Reports
Volume10
Issue number4
DOIs
Publication statusPublished - 10 Apr 2018
Externally publishedYes

Keywords

  • controlled nuclear import
  • CRM1
  • MEIS2
  • neurogenesis
  • PBX1
  • posttranslational modification
  • stem cell niche
  • subventricular zone
  • TALE-homdomain protein

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