CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles

Ivanova, Daniela; Imig, Cordelia; Camacho, Marcial; Reinhold, Annika; Guhathakurta, Debarpan; Montenegro-Venegas, Carolina; Cousin, Michael A.; Gundelfinger, Eckart D.; Rosenmund, Christian; Cooper, Benjamin H.; Fejtová, Anna

doi:10.1016/j.celrep.2020.01.079

Cited by 13 publications

(12 citation statements)

References 71 publications

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“…Lentiviral particles were produced as described ( 63 ). Human embryonic kidney 293T cells, grown in media supplemented with 10% FBS, were transfected with three plasmids FUp95GW, psPAX2, and p-CMV-VSV-G (molar ratio, 2:1:1) using Lipofectamine 2000.…”

Section: Methodsmentioning

confidence: 99%

“…The percentage of syp-mOr2, VAMP4-pHluorin, and syb2-pHluorin puncta colocalizing with PSD95-EGFP or endogenous PSD95 was determined as follows: (i) Circular ROIs with a diameter of 1.8 μm were placed manually over the nerve terminals showing accumulation of syp-mOr2, VAMP4-pHluorin, and syb2-pHluorin; (ii) the number of PSD95 puncta colocalizing with the presynaptic markers was calculated by applying an identical intensity threshold for PSD95 between the different conditions across all experiments ( 63 ).…”

Section: Methodsmentioning

confidence: 99%

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Control of synaptic vesicle release probability via VAMP4 targeting to endolysosomes

et al. 2021

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Synaptic vesicle (SV) release probability (Pr), determines the steady state and plastic control of neurotransmitter release. However, how diversity in SV composition arises and regulates the Pr of individual SVs is not understood. We found that modulation of the copy number of the noncanonical vesicular SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor), vesicle-associated membrane protein 4 (VAMP4), on SVs is key for regulating Pr. Mechanistically, this is underpinned by its reduced ability to form an efficient SNARE complex with canonical plasma membrane SNAREs. VAMP4 has unusually high synaptic turnover and is selectively sorted to endolysosomes during activity-dependent bulk endocytosis. Disruption of endolysosomal trafficking and function markedly increased the abundance of VAMP4 in the SV pool and inhibited SV fusion. Together, our results unravel a new mechanism for generating SV heterogeneity and control of Pr through coupling of SV recycling to a major clearing system that regulates protein homeostasis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Control of synaptic vesicle release probability via VAMP4 targeting to endolysosomes

et al. 2021

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“…REs are a heterogeneous population of tubulovesicular membrane-bound organelles ∼60-100 nm in diameter (Willingham and Pastan, 1980;Willingham et al, 1984). An argument against a potential link between REs and SVs is the morphological uniformity of SVs that has been observed in multiple studies and attributed to the functioning of specific endocytic mechanisms (Zhang et al, 1998;Shimizu et al, 2003;Koo et al, 2015;Ivanova et al, 2020). However, electron microscopy (EM) studies from ultrathin sections have shown that the size of SVs exists in a range from 25 to 80 nm (Fox, 1988;Harris and Sultan, 1995).…”

Section: Discussionmentioning

confidence: 99%

Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function

Ivanova

Cousin

2022

Front. Synaptic Neurosci.

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The endolysosomal system is present in all cell types. Within these cells, it performs a series of essential roles, such as trafficking and sorting of membrane cargo, intracellular signaling, control of metabolism and degradation. A specific compartment within central neurons, called the presynapse, mediates inter-neuronal communication via the fusion of neurotransmitter-containing synaptic vesicles (SVs). The localized recycling of SVs and their organization into functional pools is widely assumed to be a discrete mechanism, that only intersects with the endolysosomal system at specific points. However, evidence is emerging that molecules essential for endolysosomal function also have key roles within the SV life cycle, suggesting that they form a continuum rather than being isolated processes. In this review, we summarize the evidence for key endolysosomal molecules in SV recycling and propose an alternative model for membrane trafficking at the presynapse. This includes the hypotheses that endolysosomal intermediates represent specific functional SV pools, that sorting of cargo to SVs is mediated via the endolysosomal system and that manipulation of this process can result in both plastic changes to neurotransmitter release and pathophysiology via neurodegeneration.

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“…Interestingly, our data revealed that CtBP1 is also present in the cytoplasmic compartment of DCX + cells in the SVZ neurogenic niche in vivo. Concomitantly, CtBP1 was shown to be highly expressed in the presynaptic compartment of neurons, where it is involved in the recycling of the synaptic vesicles (Ivanova et al, 2015(Ivanova et al, , 2020. CtBP1 synapto-nuclear localization is controlled by the neuronal activity and once in the nucleus, it can control the expression of genes involved in neuroplasticity (Ivanova et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

C-Terminal Binding Proteins Promote Neurogenesis and Oligodendrogenesis in the Subventricular Zone

Serra-Almeida

Saraiva

Esteves

et al. 2021

Front. Cell Dev. Biol.

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C-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet. Herein, we evaluate the expression and functions of CtBPs in postnatal NSCs from the subventricular zone (SVZ). We found that CtBPs were expressed in immature/progenitor cells, neurons and glial cells in the SVZ niche. Using the CtBPs modulator 4-methylthio 2-oxobutyric acid (MTOB), our results showed that 1 mM of MTOB induced cell death, while 5, 25, and 50 μM increased the number of proliferating neuroblasts, mature neurons, and oligodendrocytes. Interestingly, it also increased the dendritic complexity of immature neurons. Altogether, our results highlight CtBPs putative application for brain regenerative applications.

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CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles

Cited by 13 publications

References 71 publications

Control of synaptic vesicle release probability via VAMP4 targeting to endolysosomes

Control of synaptic vesicle release probability via VAMP4 targeting to endolysosomes

Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function

C-Terminal Binding Proteins Promote Neurogenesis and Oligodendrogenesis in the Subventricular Zone

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