Prof Dr Susanne Schoch
Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells
Brain Dynamics Graduate School, Institute of Biology and Graduate Aacademy Leipzig cordially invite you to the talk:
- Prof Dr Susanne Schoch
Institute of Neuropathology, Medical Faculty, University of Bonn
"Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells"
21st August 2024, 16:20
Institute of Biology - Kleiner H?rsaal, Talstra?e 33, 04103 Leipzig
Abstract:
Full-length RIM1 and 2 are key components of the presynaptic active zone that ubiquitously control excitatory and inhibitory neurotransmitter release. Here, we report that the function of the small RIM isoform RIM4, consisting of a single C2 domain, is strikingly different from that of the long isoforms.
RIM4 is dispensable for neurotransmitter release but plays a postsynaptic, cell-type specific role in cerebellar Purkinje cells that is essential for normal motor function. In the absence of RIM4, Purkinje cell intrinsic firing is reduced and caffeine-sensitive, and dendritic integration of climbing fibre input is disturbed. Mice lacking RIM4, but not mice lacking RIM1/2, selectively in Purkinje cells exhibit a severe, hours-long paroxysmal dystonia. These episodes can also be induced by caffeine, ethanol or stress and closely resemble the deficits seen with mutations of the PNKD (paroxysmal non-kinesiogenic dystonia) gene.
Our data reveal essential postsynaptic functions of RIM proteins and show non-overlapping specialized functions of a small isoform despite high homology to a single domain in the full-length proteins.