Subcellular Localization of Cerebellar Degeneration-Related Protein 1

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background</jats:bold>: Cerebellar degeneration-related protein 1 (CDR1) is associated with paraneoplastic cerebellar degeneration – an autoimmunedisease characterized by neurodegeneration in the cerebellum. Paraneoplastic syndromes are believed to be triggered by ectopic tumour expression of neuronal proteins. The CDR1 protein is expressed by neurons in the cerebellar cortex and in certain cancers. In this study, we characterized the subcellular localization of CDR1 to help delineate potential functions in cancer cells and neurons. <jats:bold>Methods</jats:bold>: Ovarian cancer cells, cerebellar sections, and Purkinje cells in culture were immunostained and imaged by super-resolution stimulated emission depletion microscopy and potential interaction partners were investigated using a proximity ligation assay. <jats:bold>Results</jats:bold>: CDR1 was localized to the mitochondria in cancer cells and was colocalized with proteins of the outer mitochondrial membrane. Using a proximity ligation assay, we discovered that CDR1 interacts with mitofusin 1 – a transmembrane GTPase involved in mitochondrial fusion – in both cancer cells and rat cerebellum. CDR1 also colocalized with intermediate filaments, including vimentin, in cancer cells and with neurofilaments in human cerebellum. <jats:bold>Conclusion</jats:bold>: The dual localization to mitochondria and intermediate filaments as well as colocalization with key proteins involved in mitochondrial dynamics suggest that CDR1 is involved in the subcellular distribution of mitochondria in cells.</jats:p>