Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells

• DOI: 10.1093/brain/awae081
• Publication Date: 2024-03-13T20:11:14Z
• Authors: Hyuntae Kim; Nesrine Melliti; Eva Breithausen; Katrin Michel; Sara Ferrando Col...; Ekaterina Poguzhe...; Paulina Nemcova; Laura Ewell; Sandra Blaess; Albert Becker; Julika Pitsch; Dirk Dietrich; Susanne Schoch
• Keywords: Mice, Knockout; Mice, Inbred C57BL; Purkinje Cells; Mice; Dystonia; 0303 health sciences; 03 medical and health sciences; GTP-Binding Proteins; Cerebellum; Animals

Abstract Full-length RIM1 and 2 are key components of the presynaptic active zone that ubiquitously control excitatory inhibitory neurotransmitter release. Here, we report function small RIM isoform RIM4, consisting a single C2 domain, is strikingly different from long isoforms. RIM4 dispensable for release but plays postsynaptic, cell type-specific role in cerebellar Purkinje cells essential normal motor function. In absence intrinsic firing reduced caffeine-sensitive, dendritic integration climbing fibre input disturbed. Mice lacking not mice RIM1/2, selectively exhibit severe, hours-long paroxysmal dystonia. These episodes can also be induced by caffeine, ethanol or stress closely resemble deficits seen with mutations PNKD (paroxysmal non-kinesigenic dystonia) gene. Our data reveal postsynaptic functions proteins show non-overlapping specialized despite high homology to domain full-length proteins.