α-synuclein is a small protein that is mainly expressed in the synaptic terminals of nervous tissue. Although its implication in neurodegeneration is well established, the physiological role of α-synuclein remains elusive. Given its involvement in the modulation of synaptic transmission and the emerging role of microtubules at the synapse, the current study aimed at investigating whether α-synuclein becomes involved with this cytoskeletal component at the presynapse. We first analyzed the expression of α-synuclein and its colocalization with α-tubulin in murine brain. Differences were found between cortical and striatal/midbrain areas, with substantia nigra pars compacta and corpus striatum showing the lowest levels of colocalization. Using a proximity ligation assay, we revealed the direct interaction of α-synuclein with α-tubulin in murine and in human brain. Finally, the previously unexplored interaction of the two proteins in vivo at the synapse was disclosed in murine striatal presynaptic boutons through multiple approaches, from confocal spinning disk to electron microscopy. Collectively, our data strongly suggest that the association with tubulin/microtubules might actually be an important physiological function for α-synuclein in the synapse, thus suggesting its potential role in a neuropathological context.

The Association between alpha-Synuclein and alpha-Tubulin in Brain Synapses / A. Amadeo, S. Pizzi, A. Comincini, D. Modena, A.M.E. Calogero, L. Madaschi, G. Faustini, C. Rolando, A. Bellucci, G. Pezzoli, S. Mazzetti, G. Cappelletti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 9153:17(2021 Aug 25), pp. 1-22. [10.3390/ijms22179153]

The association between alpha-Synuclein and alpha-Tubulin in brain synapses

A. Amadeo
Writing – Original Draft Preparation
;
S. Pizzi
Investigation
;
A. Comincini
Formal Analysis
;
D. Modena
Investigation
;
A.M.E. Calogero
Investigation
;
L. Madaschi
Resources
;
C. Rolando
Formal Analysis
;
G. Cappelletti
Supervision
2021

Abstract

α-synuclein is a small protein that is mainly expressed in the synaptic terminals of nervous tissue. Although its implication in neurodegeneration is well established, the physiological role of α-synuclein remains elusive. Given its involvement in the modulation of synaptic transmission and the emerging role of microtubules at the synapse, the current study aimed at investigating whether α-synuclein becomes involved with this cytoskeletal component at the presynapse. We first analyzed the expression of α-synuclein and its colocalization with α-tubulin in murine brain. Differences were found between cortical and striatal/midbrain areas, with substantia nigra pars compacta and corpus striatum showing the lowest levels of colocalization. Using a proximity ligation assay, we revealed the direct interaction of α-synuclein with α-tubulin in murine and in human brain. Finally, the previously unexplored interaction of the two proteins in vivo at the synapse was disclosed in murine striatal presynaptic boutons through multiple approaches, from confocal spinning disk to electron microscopy. Collectively, our data strongly suggest that the association with tubulin/microtubules might actually be an important physiological function for α-synuclein in the synapse, thus suggesting its potential role in a neuropathological context.
microtubules; alpha-synuclein; presynaptic bouton; central nervous system; striatum; mouse; human brain; interaction; PLA; electron microscopy
Settore BIO/16 - Anatomia Umana
Settore BIO/06 - Anatomia Comparata e Citologia
Tuning Tubulin Dynamics and Interactions to Face Neurotoxicity: a Multidisciplinary Approach for Training and Research
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/874277
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