The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals
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ORIGINAL PAPER
The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals Mégane Homa 1 & Anne Loyens 1 & Sabiha Eddarkaoui 1 & Emilie Faivre 1 & Vincent Deramecourt 1 Claude-Alain Maurage 2 & Luc Buée 1 & Vincent Huin 1,3 & Bernard Sablonnière 1,3
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# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords TMEM240 . SCA21 . Cerebellum . Purkinje cell . Synapse . Immunohistochemistry
Introduction Autosomal dominant cerebellar ataxias (SCAs) constitute a clinically and genetically heterogeneous group of diseases characterized by degeneration of the cerebellum, brainstem, and spinal cord [1]. Spinocerebellar ataxia type 21 (SCA21) is defined by mild but slowly progressive cerebellar ataxia that is frequently associated with varying degrees of cognitive Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-020-01112-y) contains supplementary material, which is available to authorized users. * Vincent Huin [email protected] 1
Univ. Lille, Inserm, CHU Lille, UMR-S 1172, JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France
2
CHU Lille, Laboratoire d’Anatomopathologie, Centre de Biologie Pathologie et Génétique, F-59000 Lille, France
3
CHU Lille, Institut de Biochimie et Biologie moléculaire, Centre de Biologie Pathologie et Génétique, F-59000 Lille, France
impairment and Parkinsonism. We recently reported that SCA21 is caused by mutations in the transmembrane protein 240 (TMEM240) gene, previously called C1orf70 [2, 3]. Six missense mutations and one stop mutation in the TMEM240 gene have been described in patients in France, China, Japan, and, very recently, Germany,
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