ArticlePLoS genetics2017
RhoGEF9 splice isoforms influence neuronal maturation and synapse formation downstream of α2 GABAA receptors.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- The gephyrin scaffold modulates cortical layer 2/3 pyramidal neuron responsiveness to single whisker stimulation.Scientific reports · 2024Article
- Trophic factor BDNF inhibits GABAergic signaling by facilitating dendritic enrichment of SUMO E3 ligase PIAS3 and altering gephyrin scaffold.The Journal of biological chemistry · 2022Article
- Inhibitory postsynaptic density from the lens of phase separation.Oxford open neuroscience · 2022Review
- Mastication stimuli enhance the learning ability of weaning-stage rats, altering the hippocampal neuron transcriptome and micromorphology.Frontiers in behavioral neuroscience · 2022Article
- Review
- Identification of a Core Amino Acid Motif within the α Subunit of GABACell reports · 2019Article
- Cellular Mechanisms Contributing to the Functional Heterogeneity of GABAergic Synapses.Frontiers in molecular neuroscience · 2019Article
- Deep Survey of GABAergic Interneurons: Emerging Insights From Gene-Isoform Transcriptomics.Frontiers in molecular neuroscience · 2019Article
- Rho GTPases in Intellectual Disability: From Genetics to Therapeutic Opportunities.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In developing brain neuronal migration, dendrite outgrowth and dendritic spine outgrowth are controlled by Cdc42, a small GTPase of the Rho family, and its activators. Cdc42 function in promoting actin polymerization is crucial for glutamatergic synapse regulation. Here, we focus on GABAergic synapse-specific activator of Cdc42, collybistin (CB) and examine functional differences between its splice isoforms CB1 and CB2. We report that CB1 and CB2 differentially regulate GABAergic synapse formation in vitro along proximal-distal axis and adult-born neuron maturation in vivo. The functional specialization between CB1 and CB2 isoforms arises from their differential protein half-life, in turn regulated by ubiquitin conjugation of the unique CB1 C-terminus. We report that CB1 and CB2 negatively regulate Cdc42; however, Cdc42 activation is dependent on CB interaction with gephyrin. During hippocampal adult neurogenesis CB1 regulates neuronal migration, while CB2 is essential for dendrite outgrowth. Finally, using mice lacking Gabra2 subunit, we show that CB1 function is downstream of GABAARs, and we can rescue adult neurogenesis deficit observed in Gabra2 KO. Overall, our results uncover previously unexpected role for CB isoforms downstream of α2-containing GABAARs during neuron maturation in a Cdc42 dependent mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.