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000269354 1001_ $$0P:(DE-2719)2814190$$aJackson, Joshua$$b0$$eFirst author$$udzne
000269354 245__ $$aActin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology.
000269354 260__ $$aLondon [u.a.]$$bNature Publishing Group$$c2024
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000269354 520__ $$aAbnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson's disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function alters the number and dynamics of α-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.
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000269354 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000269354 650_7 $$2NLM Chemicals$$aWiskott-Aldrich Syndrome Protein, Neuronal
000269354 650_7 $$2NLM Chemicals$$aActins
000269354 650_7 $$2NLM Chemicals$$aWASL protein, human
000269354 650_7 $$2NLM Chemicals$$aSynapsins
000269354 650_7 $$2NLM Chemicals$$aCaenorhabditis elegans Proteins
000269354 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000269354 650_2 $$2MeSH$$aAnimals
000269354 650_2 $$2MeSH$$aHumans
000269354 650_2 $$2MeSH$$aCaenorhabditis elegans: metabolism
000269354 650_2 $$2MeSH$$aWiskott-Aldrich Syndrome Protein, Neuronal: metabolism
000269354 650_2 $$2MeSH$$aActins: metabolism
000269354 650_2 $$2MeSH$$aParkinson Disease: metabolism
000269354 650_2 $$2MeSH$$aParkinson Disease: pathology
000269354 650_2 $$2MeSH$$aSynapsins: metabolism
000269354 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: metabolism
000269354 7001_ $$0P:(DE-2719)9000582$$aHoffmann, Christian$$b1$$eFirst author
000269354 7001_ $$0P:(DE-2719)2812562$$aScifo, Enzo$$b2
000269354 7001_ $$0P:(DE-2719)9001572$$aWang, Han$$b3$$udzne
000269354 7001_ $$0P:(DE-2719)2811527$$aWischhof, Lena$$b4$$udzne
000269354 7001_ $$0P:(DE-2719)2811171$$aPiazzesi, Antonia$$b5
000269354 7001_ $$0P:(DE-2719)9001754$$aMondal, Mrityunjoy$$b6$$udzne
000269354 7001_ $$0P:(DE-2719)9002391$$aShields, Hanna$$b7$$udzne
000269354 7001_ $$aZhou, Xuesi$$b8
000269354 7001_ $$aMondin, Magali$$b9
000269354 7001_ $$aRyan, Eanna B$$b10
000269354 7001_ $$aDöring, Hermann$$b11
000269354 7001_ $$aPrehn, Jochen H M$$b12
000269354 7001_ $$aRottner, Klemens$$b13
000269354 7001_ $$aGiannone, Gregory$$b14
000269354 7001_ $$0P:(DE-2719)2010732$$aNicotera, Pierluigi$$b15$$udzne
000269354 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b16
000269354 7001_ $$0P:(DE-2719)9000670$$aMilovanovic, Dragomir$$b17
000269354 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b18$$eLast author$$udzne
000269354 773__ $$0PERI:(DE-600)2541626-1$$a10.1038/s41419-024-06686-7$$gVol. 15, no. 4, p. 304$$n4$$p304$$tCell death & disease$$v15$$x2041-4889$$y2024
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