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The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals

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A variety of missense mutations and a stop mutation in the gene coding for transmembrane protein 240 (TMEM240) have been reported to be the causative mutations of spinocerebellar ataxia 21 (SCA21). We aimed to investigate the expression of TMEM240 protein in mouse brain at the tissue, cellular, and subcellular levels. Immunofluorescence labeling showed TMEM240 to be expressed in various areas of the brain, with the highest levels in the hippocampus, isocortex, and cerebellum. In the cerebellum, TMEM240 was detected in the deep nuclei and the cerebellar cortex. The protein was expressed in all three layers of the cortex and various cerebellar neurons. TMEM240 was localized to climbing, mossy, and parallel fiber afferents projecting to Purkinje cells, as shown by co-immunostaining with VGLUT1 and VGLUT2. Co-immunostaining with synaptophysin, post-synaptic fractionation, and confirmatory electron microscopy showed TMEM240 to be localized to the post-synaptic side of synapses near the Purkinje-cell soma. Similar results were obtained in human cerebellar sections. These data suggest that TMEM240 may be involved in the organization of the cerebellar network, particularly in synaptic inputs converging on Purkinje cells. This study is the first to describe TMEM240 expression in the normal mouse brain.

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We thank the Lille NeuroBank (CHRU-Lille) for providing the human brain tissue and Nicolas Van Poucke from the Lille Biology and Pathology center. We also thank Dr. Meryem Tardivel and Antonino Bongiovanni from the cellular imagery platform for the confocal microscopy experiments. Finally, we thank Dr. Khalid Hamid El Hachimi (ICM, Paris) for his invaluable advice on interpreting the electron microscopy data.


The research leading to these results was funded by the French government’s LabEx program (“Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer’s disease”—DISTALZ), the University of Lille, the Institut National de la Santé et de la Recherche Médicale (INSERM), and the Connaître les Syndrômes Cérébelleux (CSC) charity.

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Authors and Affiliations



Mégane HOMA: Had a major role in the acquisition of data, including all immunohistochemical analyses, interpreted the data, and drafted the manuscript.

Anne LOYENS: Had a major role in the acquisition of the transmission electron micrographs.

Sabiha EDDARKAOUI: Had a major role in the production of a new polyclonal antibody.

Emilie FAIVRE: Had a major role in animal and tissue preparation. Revised the manuscript for critical intellectual content.

Vincent DERAMECOURT and Claude-Alain MAURAGE: Supply of human cerebellar samples. Selection of images.

Luc BUÉE: Revised the manuscript for critical intellectual content.

Vincent HUIN and Bernard SABLONNIÈRE: Interpreted the data and revised the manuscript for critical intellectual content.

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Correspondence to Vincent Huin.

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Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. Experimental protocols were approved by the local animal ethical committee (approval APAFIS#2264-2015101320441671 from CEEA75, Lille, France). Human brains were obtained from the Lille Neurobank (CRB/CIC1403 Biobank, BB-0033-00030, agreement DC-2008-642), which fulfills the criteria of the local laws and regulations on biological resources with donor consent, data protection, and ethical committee review.

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The authors declare that they have no conflicts of interest.

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Homa, M., Loyens, A., Eddarkaoui, S. et al. The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals. Cerebellum 19, 358–369 (2020).

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