The neuronal transcription factor MEIS2 is a calpain-2 protease target
© 2024. Published by The Company of Biologists Ltd..
Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular-subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1). Phosphorylation at conserved serine and/or threonine residues, or dimerization with PBX1, reduced the sensitivity of MEIS2 towards cleavage by calpain-2. In the adult V-SVZ, calpain-2 activity is high in stem and progenitor cells, but rapidly declines during neuronal differentiation, which is accompanied by increased stability of MEIS2 full-length protein. In accordance with this, blocking calpain-2 activity in stem and progenitor cells, or overexpression of a cleavage-insensitive form of MEIS2, increased the production of neurons, whereas overexpression of a catalytically active CAPN2 reduced it. Collectively, our results support a key role for calpain-2 in controlling the output of adult V-SVZ neural stem and progenitor cells through cleavage of the neuronal fate determinant MEIS2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:137 |
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| Enthalten in: |
Journal of cell science - 137(2024), 4 vom: 15. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Müller, Tanja [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.02.2024 Date Revised 17.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1242/jcs.261482 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367950928 |
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| 100 | 1 | |a Müller, Tanja |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The neuronal transcription factor MEIS2 is a calpain-2 protease target |
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| 500 | |a Date Revised 17.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. Published by The Company of Biologists Ltd. | ||
| 520 | |a Tight control over transcription factor activity is necessary for a sensible balance between cellular proliferation and differentiation in the embryo and during tissue homeostasis by adult stem cells, but mechanistic details have remained incomplete. The homeodomain transcription factor MEIS2 is an important regulator of neurogenesis in the ventricular-subventricular zone (V-SVZ) adult stem cell niche in mice. We here identify MEIS2 as direct target of the intracellular protease calpain-2 (composed of the catalytic subunit CAPN2 and the regulatory subunit CAPNS1). Phosphorylation at conserved serine and/or threonine residues, or dimerization with PBX1, reduced the sensitivity of MEIS2 towards cleavage by calpain-2. In the adult V-SVZ, calpain-2 activity is high in stem and progenitor cells, but rapidly declines during neuronal differentiation, which is accompanied by increased stability of MEIS2 full-length protein. In accordance with this, blocking calpain-2 activity in stem and progenitor cells, or overexpression of a cleavage-insensitive form of MEIS2, increased the production of neurons, whereas overexpression of a catalytically active CAPN2 reduced it. Collectively, our results support a key role for calpain-2 in controlling the output of adult V-SVZ neural stem and progenitor cells through cleavage of the neuronal fate determinant MEIS2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adult neurogenesis | |
| 650 | 4 | |a Calpain | |
| 650 | 4 | |a MEIS homeodomain protein | |
| 650 | 4 | |a Stem cell | |
| 650 | 4 | |a Subventricular zone | |
| 650 | 4 | |a Transcription factor | |
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| 700 | 1 | |a Reichlmeir, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Hau, Ann-Christin |e verfasserin |4 aut | |
| 700 | 1 | |a Wittig, Ilka |e verfasserin |4 aut | |
| 700 | 1 | |a Schulte, Dorothea |e verfasserin |4 aut | |
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