The ubiquitin ligase Ariadne-1 regulates neurotransmitter release via ubiquitination of NSF

Ramírez, Juanma; Morales, Miguel; Osinalde, Nerea; Martinez-Padron, Imanol; Mayor, Ugo; Ferrús, Alberto

doi:10.1016/j.jbc.2021.100408

Cited by 11 publications

(7 citation statements)

References 76 publications

(140 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GFP pulldowns were performed as previously described 46 , 47 , 99 , 104 . Briefly, cells were lysed with 300 µl of lysis buffer and centrifuged at 14,000 g at 4 °C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome

et al. 2023

Self Cite

View full text Add to dashboard Cite

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss of UBE3A decreases actin filaments and reduces PIEZO2 expression and function. A linoleic acid (LA)-enriched diet increases PIEZO2 activity, mechano-excitability, and improves gait in male AS mice. Finally, LA supplementation increases PIEZO2 function in stem cell-derived neurons from individuals with AS. We propose a mechanism whereby loss of UBE3A expression reduces PIEZO2 function and identified a fatty acid that enhances channel activity and ameliorates AS-associated mechano-sensory deficits.

show abstract

“…GFP pulldowns were performed as previously described 46 , 47 , 99 , 104 . Briefly, cells were lysed with 300 µl of lysis buffer and centrifuged at 14,000 g at 4 °C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…First applied in vivo in Drosophila, this approach allowed the identification of hundreds of ubiquitin conjugates from the fly nervous system by LC-MS. [10,11] More recently, it has proven useful for the identification of E3 ligase or DUB substrates. [12,11,13,14] Beyond Ub, a set of tools was developed to study each and every UbL. [15] Overall, specific BirA-mediated biotinylation of the AviTag is a versatile and powerful tool for studying Ub/UbL modifications (Figure 2).…”

Section: Identification Of Subproteomes Covalently Modified By Ub or ...mentioning

confidence: 99%

Biotin‐Based Strategies to Explore the World of Ubiquitin and Ubiquitin‐Like Modifiers

Merino‐Cacho,

Barroso‐Gomila,

Hernández‐Sánchez

et al. 2024

ChemBioChem

Self Cite

View full text Add to dashboard Cite

A complex code of cellular signals is mediated by ubiquitin and ubiquitin‐like (Ub/UbL) modifications on substrate proteins. The so‐called Ubiquitin Code specifies protein fates, such as stability, subcellular localization, functional activation or suppression, and interactions. Hundreds of enzymes are involved in placing and removing Ub/UbL on thousands of substrates, while the consequences of modifications and the mechanisms of specificity are still poorly defined. Challenges include rapid and transient engagement of enzymes and Ub/UbL interactors, low stoichiometry of modified versus non‐modified cellular substrates, and protease‐mediated loss of Ub/UbL in lysates. To decipher this complexity and confront the challenges, many tools have been created to trap and identify substrates and interactors linked to Ub/UbL modification. This review focuses on an assortment of biotin‐based tools we have developed for this purpose (for example BioUbLs, UbL‐ID, BioE3), taking advantage of the strong affinity of biotin‐streptavidin and the stringent lysis/washing approach allowed by it, paired with sensitive mass‐spectrometry‐based proteomic methods. Knowing how substrates change during development and disease, the consequences of substrate modification, and matching substrates to particular UbL‐ligating enzymes will contribute new insights into how Ub/UbL signaling works and how it can be exploited for therapies.

show abstract

“…However, our understanding of the role of E3 ligases in the regulation of synaptic transmission is very limited. While several E3 ligases have been linked to postsynaptic forms of synaptic plasticity ( Hegde, 2010 ), only three E3 ligases, Scrapper ( Yao et al, 2007 ), Highwire ( Russo et al, 2019 ), and Ariadne-1 ( Ramírez et al, 2021 ) have been implicated in the regulation of presynaptic function. Moreover, a systematic investigation of E3 ligase function in the context of synaptic transmission is lacking.…”

Section: Introductionmentioning

confidence: 99%

The E3 ligase Thin controls homeostatic plasticity through neurotransmitter release repression

Baccino-Calace

Schmidt

Müller

2022

eLife

View full text Add to dashboard Cite

Synaptic proteins and synaptic transmission are under homeostatic control, but the relationship between these two processes remains enigmatic. Here, we systematically investigated the role of E3 ubiquitin ligases, key regulators of protein degradation-mediated proteostasis, in presynaptic homeostatic plasticity (PHP). An electrophysiology-based genetic screen of 157 E3 ligase-encoding genes at the Drosophila neuromuscular junction identified thin, an ortholog of human tripartite motif-containing 32 (TRIM32), a gene implicated in several neurological disorders, including autism spectrum disorder and schizophrenia. We demonstrate that thin functions presynaptically during rapid and sustained PHP. Presynaptic thin negatively regulates neurotransmitter release under baseline conditions by limiting the number of release-ready vesicles, largely independent of gross morphological defects. We provide genetic evidence that thin controls release through dysbindin, a schizophrenia-susceptibility gene required for PHP. Thin and Dysbindin localize in proximity within presynaptic boutons, and Thin degrades Dysbindin in vitro. Thus, the E3 ligase Thin links protein degradation-dependent proteostasis of Dysbindin to homeostatic regulation of neurotransmitter release.

show abstract

The ubiquitin ligase Ariadne-1 regulates neurotransmitter release via ubiquitination of NSF

Cited by 11 publications

References 76 publications

Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome

Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome

Biotin‐Based Strategies to Explore the World of Ubiquitin and Ubiquitin‐Like Modifiers

The E3 ligase Thin controls homeostatic plasticity through neurotransmitter release repression

Contact Info

Product

Resources

About