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CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
- Source :
- Cell Reports, Vol 30, Iss 7, Pp 2444-2459.e7 (2020), Cell Reports, Cell reports, 30(7):2444-2459.e7, Ivanova, D, Imig, C, Camacho, M, Reinhold, A, Guhathakurta, D, Montenegro-Venegas, C, Cousin, M A, Gundelfinger, E D, Rosenmund, C, Cooper, B & Fejtova, A 2020, ' CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles ', Cell Reports, vol. 30, no. 7, pp. 2444-2459.e7 . https://doi.org/10.1016/j.celrep.2020.01.079
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Summary Compensatory endocytosis of released synaptic vesicles (SVs) relies on coordinated signaling at the lipid-protein interface. Here, we address the synaptic function of C-terminal binding protein 1 (CtBP1), a ubiquitous regulator of gene expression and membrane trafficking in cultured hippocampal neurons. In the absence of CtBP1, synapses form in greater density and show changes in SV distribution and size. The increased basal neurotransmission and enhanced synaptic depression could be attributed to a higher vesicular release probability and a smaller fraction of release-competent SVs, respectively. Rescue experiments with specifically targeted constructs indicate that, while synaptogenesis and release probability are controlled by nuclear CtBP1, the efficient recycling of SVs relies on its synaptic expression. The ability of presynaptic CtBP1 to facilitate compensatory endocytosis depends on its membrane-fission activity and the activation of the lipid-metabolizing enzyme PLD1. Thus, CtBP1 regulates SV recycling by promoting a permissive lipid environment for compensatory endocytosis.<br />Graphical Abstract<br />Highlights • Nuclear CtBP1 restricts synaptogenesis and vesicular release probability • CtBP1 is required for efficient compensatory endocytosis at the presynapse • CtBP1 facilitates synaptic vesicle retrieval via activation of the lipid enzyme PLD1 • Phosphorylation by Pak1 shifts CtBP1 from the active zone to endocytic sites<br />Ivanova et al. demonstrate a dual role of CtBP1 in synaptic transmission. Nuclear CtBP1 restricts synaptogenesis and vesicular release probability, whereas presynaptic CtBP1 promotes compensatory endocytosis via activation of the lipid enzyme PLD1. Phosphorylation by Pak1 controls the redistribution of CtBP1 from active zones toward endocytic sites linking presynaptic exo- and endocytosis.
- Subjects :
- 0301 basic medicine
PLD1
membrane fission
Synaptogenesis
CtBP1
exo-endocytosis coupling
synaptic vesicle pools
Pak1
presynapse
compensatory endocytosis
Bassoon
synaptic vesicle recycling
Neurotransmission
Endocytosis
Synaptic vesicle
General Biochemistry, Genetics and Molecular Biology
Presynapse
Article
03 medical and health sciences
0302 clinical medicine
PAK1
Membrane fission
Synaptic vesicle recycling
Humans
lcsh:QH301-705.5
Neurons
Chemistry
Cell biology
DNA-Binding Proteins
Alcohol Oxidoreductases
030104 developmental biology
lcsh:Biology (General)
Synaptic Vesicles
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 30
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....eec9a3afacebcf2e7ee3967bfddcf2dd