Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis

Tripartite motif 2 (TRIM2) drives neurite outgrowth and polarization, is involved in axon specification, and confers neuroprotective functions during rapid ischemia. The mechanisms controlling neuronal cell fate determination and differentiation are fundamental for neural development. Here, we show...

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Main Authors: Ashwin Lokapally, Herbert Neuhaus, Juliane Herfurth, Thomas Hollemann
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/7/1734
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author Ashwin Lokapally
Herbert Neuhaus
Juliane Herfurth
Thomas Hollemann
author_facet Ashwin Lokapally
Herbert Neuhaus
Juliane Herfurth
Thomas Hollemann
author_sort Ashwin Lokapally
collection DOAJ
description Tripartite motif 2 (TRIM2) drives neurite outgrowth and polarization, is involved in axon specification, and confers neuroprotective functions during rapid ischemia. The mechanisms controlling neuronal cell fate determination and differentiation are fundamental for neural development. Here, we show that in <i>Xenopus</i>, <i>trim2</i> knockdown affects primary neurogenesis and neural progenitor cell survival. Embryos also suffer from severe craniofacial malformation, a reduction in brain volume, and the loss of motor sensory function. Using a high-throughput LC-MS/MS approach with GST-Trim2 as bait, we pulled down ALG-2 interacting protein X (Alix) from <i>Xenopus</i> embryonic lysates. We demonstrate that the expression of <i>trim2</i>/TRIM2 and <i>alix</i>/ALIX overlap during larval development and on a cellular level in cell culture. Interestingly, <i>trim2</i> morphants showed a clustering and apoptosis of neural progenitors, which are phenotypic hallmarks that are also observed in Alix KO mice. Therefore, we propose that the interaction of Alix and Trim2 plays a key role in the determination and differentiation of neural progenitors via the modulation of cell proliferation/apoptosis during neurogenesis.
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spelling doaj.art-b65f87634aa541e8846a6b2341bf6f3f2023-11-20T07:21:28ZengMDPI AGCells2073-44092020-07-0197173410.3390/cells9071734Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early NeurogenesisAshwin Lokapally0Herbert Neuhaus1Juliane Herfurth2Thomas Hollemann3Institute for Physiological Chemistry, Martin-Luther University Halle-Wittenberg, Hollystrasse 1, 06114 Halle, GermanyInstitute for Physiological Chemistry, Martin-Luther University Halle-Wittenberg, Hollystrasse 1, 06114 Halle, GermanyInstitute for Physiological Chemistry, Martin-Luther University Halle-Wittenberg, Hollystrasse 1, 06114 Halle, GermanyInstitute for Physiological Chemistry, Martin-Luther University Halle-Wittenberg, Hollystrasse 1, 06114 Halle, GermanyTripartite motif 2 (TRIM2) drives neurite outgrowth and polarization, is involved in axon specification, and confers neuroprotective functions during rapid ischemia. The mechanisms controlling neuronal cell fate determination and differentiation are fundamental for neural development. Here, we show that in <i>Xenopus</i>, <i>trim2</i> knockdown affects primary neurogenesis and neural progenitor cell survival. Embryos also suffer from severe craniofacial malformation, a reduction in brain volume, and the loss of motor sensory function. Using a high-throughput LC-MS/MS approach with GST-Trim2 as bait, we pulled down ALG-2 interacting protein X (Alix) from <i>Xenopus</i> embryonic lysates. We demonstrate that the expression of <i>trim2</i>/TRIM2 and <i>alix</i>/ALIX overlap during larval development and on a cellular level in cell culture. Interestingly, <i>trim2</i> morphants showed a clustering and apoptosis of neural progenitors, which are phenotypic hallmarks that are also observed in Alix KO mice. Therefore, we propose that the interaction of Alix and Trim2 plays a key role in the determination and differentiation of neural progenitors via the modulation of cell proliferation/apoptosis during neurogenesis.https://www.mdpi.com/2073-4409/9/7/1734Trim2Alix<i>Xenopus</i>neural developmentneural differentiationapoptosis
spellingShingle Ashwin Lokapally
Herbert Neuhaus
Juliane Herfurth
Thomas Hollemann
Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis
Cells
Trim2
Alix
<i>Xenopus</i>
neural development
neural differentiation
apoptosis
title Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis
title_full Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis
title_fullStr Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis
title_full_unstemmed Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis
title_short Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis
title_sort interplay of trim2 e3 ubiquitin ligase and alix escrt complex control of developmental plasticity during early neurogenesis
topic Trim2
Alix
<i>Xenopus</i>
neural development
neural differentiation
apoptosis
url https://www.mdpi.com/2073-4409/9/7/1734
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AT julianeherfurth interplayoftrim2e3ubiquitinligaseandalixescrtcomplexcontrolofdevelopmentalplasticityduringearlyneurogenesis
AT thomashollemann interplayoftrim2e3ubiquitinligaseandalixescrtcomplexcontrolofdevelopmentalplasticityduringearlyneurogenesis