Synapsin E-domain is essential for α-synuclein function

Stavsky, Alexandra; Parra-Rivas, Leonardo A.; Tal, Shani; Madhivanan, Kayalvizhi; Roy, Subhojit; Gitler, Daniel

doi:10.1101/2023.06.24.546170

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…Through interaction with several of these proteins, α-syn regulates SNARE complex assembly and exocytosis [72,[74][75][76]87]. Work from the laboratories of Roy and Gitler suggests that the synapsins also act as key regulators of the synaptic effects of α-syn [88,89]. The interaction between α-syn and these release-regulating proteins provides a potential mechanism through which α-syn affects neurotransmitter release in health and pathology.…”

Section: General Mechanisms Of Synaptic α-Synucleinmentioning

confidence: 99%

From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein

Nordengen,

Morland

2024

IJMS

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Alpha-synuclein (α-syn) has gained significant attention due to its involvement in neurodegenerative diseases, particularly Parkinson’s disease. However, its normal function in the human brain is equally fascinating. The α-syn protein is highly dynamic and can adapt to various conformational stages, which differ in their interaction with synaptic elements, their propensity to drive pathological aggregation, and their toxicity. This review will delve into the multifaceted role of α-syn in different types of synapses, shedding light on contributions to neurotransmission and overall brain function. We describe the physiological role of α-syn at central synapses, including the bidirectional interaction between α-syn and neurotransmitter systems.

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Section: General Mechanisms Of Synaptic α-Synucleinmentioning

confidence: 99%

From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein

Nordengen,

Morland

2024

IJMS

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Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles

Longfield,

Gormal,

Feller

et al. 2024

Nat Commun

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Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism. Here, we used Dual-pulse sub-diffractional Tracking of Internalised Molecules (DsdTIM) to simultaneously track single SVs from the recycling and the reserve pools, in live hippocampal neurons. The reserve pool displays a lower presynaptic mobility compared to the recycling pool and is also present in the axons. Triple knockout of Synapsin 1-3 genes (SynTKO) increased the mobility of reserve pool SVs. Re-expression of wild-type Syn2a (Syn2aWT), but not the tetramerization-deficient mutant K337Q (Syn2aK337Q), fully rescued these effects. Single-particle tracking revealed that Syn2aK337QmEos3.1 exhibited altered activity-dependent presynaptic translocation and nanoclustering. Therefore, Syn2a tetramerization controls its own presynaptic nanoclustering and thereby contributes to the dynamic immobilisation of the SV reserve pool.

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Synapsin E-domain is essential for α-synuclein function

Cited by 2 publications

References 34 publications

From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein

From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein

Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles

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