Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks
© 2021. The Author(s)..
SORCS2 is one of five proteins that constitute the Vps10p-domain receptor family. Members of this family play important roles in cellular processes linked to neuronal survival, differentiation and function. Genetic and functional studies implicate SORCS2 in cognitive function, as well as in neurodegenerative and psychiatric disorders. DNA damage and DNA repair deficits are linked to ageing and neurodegeneration, and transient neuronal DNA double-strand breaks (DSBs) also occur as a result of neuronal activity. Here, we report a novel role for SORCS2 in DSB formation. We show that SorCS2 loss is associated with elevated DSB levels in the mouse dentate gyrus and that knocking out SORCS2 in a human neuronal cell line increased Topoisomerase IIβ-dependent DSB formation and reduced neuronal viability. Neuronal stimulation had no impact on levels of DNA breaks in vitro, suggesting that the observed differences may not be the result of aberrant neuronal activity in these cells. Our findings are consistent with studies linking the VPS10 receptors and DNA damage to neurodegenerative conditions.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
|---|---|
| Enthalten in: |
Cellular and molecular neurobiology - 43(2023), 1 vom: 06. Jan., Seite 237-249 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gospodinova, Katerina O [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
DNA double-strand breaks |
|---|
| Anmerkungen: |
Date Completed 06.01.2023 Date Revised 11.01.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s10571-021-01163-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM332797546 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM332797546 | ||
| 003 | DE-627 | ||
| 005 | 20231225220320.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10571-021-01163-7 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1109.xml |
| 035 | |a (DE-627)NLM332797546 | ||
| 035 | |a (NLM)34741697 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gospodinova, Katerina O |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.01.2023 | ||
| 500 | |a Date Revised 11.01.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a SORCS2 is one of five proteins that constitute the Vps10p-domain receptor family. Members of this family play important roles in cellular processes linked to neuronal survival, differentiation and function. Genetic and functional studies implicate SORCS2 in cognitive function, as well as in neurodegenerative and psychiatric disorders. DNA damage and DNA repair deficits are linked to ageing and neurodegeneration, and transient neuronal DNA double-strand breaks (DSBs) also occur as a result of neuronal activity. Here, we report a novel role for SORCS2 in DSB formation. We show that SorCS2 loss is associated with elevated DSB levels in the mouse dentate gyrus and that knocking out SORCS2 in a human neuronal cell line increased Topoisomerase IIβ-dependent DSB formation and reduced neuronal viability. Neuronal stimulation had no impact on levels of DNA breaks in vitro, suggesting that the observed differences may not be the result of aberrant neuronal activity in these cells. Our findings are consistent with studies linking the VPS10 receptors and DNA damage to neurodegenerative conditions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DNA double-strand breaks | |
| 650 | 4 | |a Neurodegeneration | |
| 650 | 4 | |a Neuronal activity | |
| 650 | 4 | |a SORCS2 | |
| 650 | 7 | |a SORCS2 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a SorCS2 protein, mouse |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 700 | 1 | |a Olsen, Ditte |e verfasserin |4 aut | |
| 700 | 1 | |a Kaas, Mathias |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Susan M |e verfasserin |4 aut | |
| 700 | 1 | |a Phillips, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Rosie M |e verfasserin |4 aut | |
| 700 | 1 | |a Bermingham, Mairead L |e verfasserin |4 aut | |
| 700 | 1 | |a Payne, Abigail L |e verfasserin |4 aut | |
| 700 | 1 | |a Giannopoulos, Panagiotis |e verfasserin |4 aut | |
| 700 | 1 | |a Pandya, Divya |e verfasserin |4 aut | |
| 700 | 1 | |a Spires-Jones, Tara L |e verfasserin |4 aut | |
| 700 | 1 | |a Abbott, Catherine M |e verfasserin |4 aut | |
| 700 | 1 | |a Porteous, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Glerup, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Evans, Kathryn L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cellular and molecular neurobiology |d 1993 |g 43(2023), 1 vom: 06. Jan., Seite 237-249 |w (DE-627)NLM012620580 |x 1573-6830 |7 nnns |
| 773 | 1 | 8 | |g volume:43 |g year:2023 |g number:1 |g day:06 |g month:01 |g pages:237-249 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s10571-021-01163-7 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 43 |j 2023 |e 1 |b 06 |c 01 |h 237-249 | ||