A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity.
Rem2 is a member of the RGK family of small Ras-like GTPases whose expression and function is regulated by neuronal activity in the brain. A number of questions still remain as to the endogenous functions of Rem2 in neurons. RNAi-mediated Rem2 knockdown leads to an increase in dendritic complexity a...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3753333?pdf=render |
| _version_ | 1818506008433000448 |
|---|---|
| author | Anna R Moore Amy E Ghiretti Suzanne Paradis |
| author_facet | Anna R Moore Amy E Ghiretti Suzanne Paradis |
| author_sort | Anna R Moore |
| collection | DOAJ |
| description | Rem2 is a member of the RGK family of small Ras-like GTPases whose expression and function is regulated by neuronal activity in the brain. A number of questions still remain as to the endogenous functions of Rem2 in neurons. RNAi-mediated Rem2 knockdown leads to an increase in dendritic complexity and a decrease in functional excitatory synapses, though a recent report challenged the specificity of Rem2-targeted RNAi reagents. In addition, overexpression in a number of cell types has shown that Rem2 can inhibit voltage-gated calcium channel (VGCC) function, while studies employing RNAi-mediated knockdown of Rem2 have failed to observe a corresponding enhancement of VGCC function. To further investigate these discrepancies and determine the endogenous function of Rem2, we took a comprehensive, loss-of-function approach utilizing two independent, validated Rem2-targeted shRNAs to analyze Rem2 function. We sought to investigate the consequence of endogenous Rem2 knockdown by focusing on the three reported functions of Rem2 in neurons: regulation of synapse formation, dendritic morphology, and voltage-gated calcium channels. We conclude that endogenous Rem2 is a positive regulator of functional, excitatory synapse development and a negative regulator of dendritic complexity. In addition, while we are unable to reach a definitive conclusion as to whether the regulation of VGCCs is an endogenous function of Rem2, our study reports important data regarding RNAi reagents for use in future investigation of this issue. |
| first_indexed | 2024-12-10T21:58:37Z |
| format | Article |
| id | doaj.art-ab48b1a1d51740a19a426a419c115afd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T21:58:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ab48b1a1d51740a19a426a419c115afd2022-12-22T01:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7475110.1371/journal.pone.0074751A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity.Anna R MooreAmy E GhirettiSuzanne ParadisRem2 is a member of the RGK family of small Ras-like GTPases whose expression and function is regulated by neuronal activity in the brain. A number of questions still remain as to the endogenous functions of Rem2 in neurons. RNAi-mediated Rem2 knockdown leads to an increase in dendritic complexity and a decrease in functional excitatory synapses, though a recent report challenged the specificity of Rem2-targeted RNAi reagents. In addition, overexpression in a number of cell types has shown that Rem2 can inhibit voltage-gated calcium channel (VGCC) function, while studies employing RNAi-mediated knockdown of Rem2 have failed to observe a corresponding enhancement of VGCC function. To further investigate these discrepancies and determine the endogenous function of Rem2, we took a comprehensive, loss-of-function approach utilizing two independent, validated Rem2-targeted shRNAs to analyze Rem2 function. We sought to investigate the consequence of endogenous Rem2 knockdown by focusing on the three reported functions of Rem2 in neurons: regulation of synapse formation, dendritic morphology, and voltage-gated calcium channels. We conclude that endogenous Rem2 is a positive regulator of functional, excitatory synapse development and a negative regulator of dendritic complexity. In addition, while we are unable to reach a definitive conclusion as to whether the regulation of VGCCs is an endogenous function of Rem2, our study reports important data regarding RNAi reagents for use in future investigation of this issue.http://europepmc.org/articles/PMC3753333?pdf=render |
| spellingShingle | Anna R Moore Amy E Ghiretti Suzanne Paradis A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity. PLoS ONE |
| title | A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity. |
| title_full | A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity. |
| title_fullStr | A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity. |
| title_full_unstemmed | A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity. |
| title_short | A loss-of-function analysis reveals that endogenous Rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity. |
| title_sort | loss of function analysis reveals that endogenous rem2 promotes functional glutamatergic synapse formation and restricts dendritic complexity |
| url | http://europepmc.org/articles/PMC3753333?pdf=render |
| work_keys_str_mv | AT annarmoore alossoffunctionanalysisrevealsthatendogenousrem2promotesfunctionalglutamatergicsynapseformationandrestrictsdendriticcomplexity AT amyeghiretti alossoffunctionanalysisrevealsthatendogenousrem2promotesfunctionalglutamatergicsynapseformationandrestrictsdendriticcomplexity AT suzanneparadis alossoffunctionanalysisrevealsthatendogenousrem2promotesfunctionalglutamatergicsynapseformationandrestrictsdendriticcomplexity AT annarmoore lossoffunctionanalysisrevealsthatendogenousrem2promotesfunctionalglutamatergicsynapseformationandrestrictsdendriticcomplexity AT amyeghiretti lossoffunctionanalysisrevealsthatendogenousrem2promotesfunctionalglutamatergicsynapseformationandrestrictsdendriticcomplexity AT suzanneparadis lossoffunctionanalysisrevealsthatendogenousrem2promotesfunctionalglutamatergicsynapseformationandrestrictsdendriticcomplexity |