Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its Expression Article Swipe
Lingfei Li
,
Philip Wing‐Lok Ho
,
Huifang Liu
,
Shirley Yin-Yu Pang
,
Eunice Eun-Seo Chang
,
Zoe Yuen-Kiu Choi
,
Yasine Malki
,
Michelle Hiu-Wai Kung
,
D. Ramsden
,
Shu‐Leong Ho
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/ijms23073646
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/ijms23073646
Synaptogyrin-3 (SYNGR3) is a synaptic vesicular membrane protein. Amongst four homologues (SYNGR1 to 4), SYNGR1 and 3 are especially abundant in the brain. SYNGR3 interacts with the dopamine transporter (DAT) to facilitate dopamine (DA) uptake and synaptic DA turnover in dopaminergic transmission. Perturbed SYNGR3 expression is observed in Parkinson’s disease (PD). The regulatory elements which affect SYNGR3 expression are unknown. Nuclear-receptor-related-1 protein (NURR1) can regulate dopaminergic neuronal differentiation and maintenance via binding to NGFI-B response elements (NBRE). We explored whether NURR1 can regulate SYNGR3 expression using an in silico analysis of the 5′-flanking region of the human SYNGR3 gene, reporter gene activity and an electrophoretic mobility shift assay (EMSA) of potential cis-acting sites. In silico analysis of two genomic DNA segments (1870 bp 5′-flanking region and 1870 + 159 bp of first exon) revealed one X Core Promoter Element 1 (XCPE1), two SP1, and three potential non-canonical NBRE response elements (ncNBRE) but no CAAT or TATA box. The longer segment exhibited gene promoter activity in luciferase reporter assays. Site-directed mutagenesis of XCPE1 decreased promoter activity in human neuroblastoma SH-SY5Y (↓43.2%) and human embryonic kidney HEK293 cells (↓39.7%). EMSA demonstrated NURR1 binding to these three ncNBRE. Site-directed mutagenesis of these ncNBRE reduced promoter activity by 11–17% in SH-SY5Y (neuronal) but not in HEK293 (non-neuronal) cells. C-DIM12 (Nurr1 activator) increased SYNGR3 protein expression in SH-SY5Y cells and its promoter activity using a real-time luciferase assay. As perturbed vesicular function is a feature of major neurodegenerative diseases, inducing SYNGR3 expression by NURR1 activators may be a potential therapeutic target to attenuate synaptic dysfunction in PD.
Related Topics
Concepts
Electrophoretic mobility shift assay
Reporter gene
Biology
Molecular biology
HEK 293 cells
Ectopic expression
Gene expression
Activator (genetics)
Transcription factor
Cell biology
Gene
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms23073646
- https://www.mdpi.com/1422-0067/23/7/3646/pdf?version=1648297597
- OA Status
- gold
- Cited By
- 9
- References
- 65
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4220743170
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4220743170Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms23073646Digital Object Identifier
- Title
-
Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its ExpressionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-03-26Full publication date if available
- Authors
-
Lingfei Li, Philip Wing‐Lok Ho, Huifang Liu, Shirley Yin-Yu Pang, Eunice Eun-Seo Chang, Zoe Yuen-Kiu Choi, Yasine Malki, Michelle Hiu-Wai Kung, D. Ramsden, Shu‐Leong HoList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms23073646Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/23/7/3646/pdf?version=1648297597Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/23/7/3646/pdf?version=1648297597Direct OA link when available
- Concepts
-
Electrophoretic mobility shift assay, Reporter gene, Biology, Molecular biology, HEK 293 cells, Ectopic expression, Gene expression, Activator (genetics), Transcription factor, Cell biology, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
9Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 2, 2023: 4Per-year citation counts (last 5 years)
- References (count)
-
65Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.synaptic | 4, 36, 258 |
| abstract_inverted_index.turnover | 38 |
| abstract_inverted_index.unknown. | 59 |
| abstract_inverted_index.Perturbed | 42 |
| abstract_inverted_index.attenuate | 257 |
| abstract_inverted_index.decreased | 172 |
| abstract_inverted_index.diseases, | 243 |
| abstract_inverted_index.embryonic | 182 |
| abstract_inverted_index.exhibited | 160 |
| abstract_inverted_index.increased | 217 |
| abstract_inverted_index.interacts | 24 |
| abstract_inverted_index.perturbed | 234 |
| abstract_inverted_index.potential | 110, 145, 253 |
| abstract_inverted_index.real-time | 230 |
| abstract_inverted_index.vesicular | 5, 235 |
| abstract_inverted_index.(neuronal) | 207 |
| abstract_inverted_index.(↓43.2%) | 179 |
| abstract_inverted_index.activator) | 216 |
| abstract_inverted_index.activators | 249 |
| abstract_inverted_index.cis-acting | 111 |
| abstract_inverted_index.especially | 18 |
| abstract_inverted_index.expression | 44, 57, 84, 220, 246 |
| abstract_inverted_index.facilitate | 31 |
| abstract_inverted_index.homologues | 10 |
| abstract_inverted_index.luciferase | 165, 231 |
| abstract_inverted_index.regulatory | 52 |
| abstract_inverted_index.(↓39.7%). | 186 |
| abstract_inverted_index.dysfunction | 259 |
| abstract_inverted_index.maintenance | 69 |
| abstract_inverted_index.mutagenesis | 169, 196 |
| abstract_inverted_index.therapeutic | 254 |
| abstract_inverted_index.transporter | 28 |
| abstract_inverted_index.demonstrated | 188 |
| abstract_inverted_index.dopaminergic | 40, 65 |
| abstract_inverted_index.5′-flanking | 92, 123 |
| abstract_inverted_index.Parkinson’s | 48 |
| abstract_inverted_index.Site-directed | 168, 195 |
| abstract_inverted_index.neuroblastoma | 177 |
| abstract_inverted_index.non-canonical | 146 |
| abstract_inverted_index.transmission. | 41 |
| abstract_inverted_index.(non-neuronal) | 212 |
| abstract_inverted_index.Synaptogyrin-3 | 0 |
| abstract_inverted_index.differentiation | 67 |
| abstract_inverted_index.electrophoretic | 104 |
| abstract_inverted_index.neurodegenerative | 242 |
| abstract_inverted_index.Nuclear-receptor-related-1 | 60 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5111710941, https://openalex.org/A5035437162 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I79619799, https://openalex.org/I889458895 |
| citation_normalized_percentile.value | 0.71721719 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |