Dynamics of local presynaptic protein synthesis of active zone components in spinal motoneurons

• Applicants: Professor Dr. Markus Sauer; Professor Dr. Michael A. Sendtner
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405988308

Local protein synthesis in axon terminals plays a central role in axon guidance, postnatal differentiation of active zones and possibly also in synaptic plasticity of neuromuscular endplates. We have determined axonal transcriptomes in embryonic motoneurons and alterations of these transcriptomes in motoneurons from a mouse model of spinal muscular atrophy, the predominant form of motoneuron disease in children and young adults. Whereas the mRNAs for major active zone components such as Bassoon and Piccolo are mainly found in the somatodendritic compartments, the mRNA for Munc13-2 and Liprin-alpha-1 are highly enriched in axons and axonal terminals. Moreover, we found that the mRNAs encoding synaptophysin and VAMP2 are highly upregulated in the axonal compartment of Smn-deficient motoneurons. The goal of this project is to investigate the specific role of local translation of Munc13-2 in axon terminals of spinal motoneurons and to characterize the potential role of local Munc13-2 in disturbed synaptic function at neuromuscular endplates in spinal muscular atrophy. We expect new insights into the dynamics of local protein synthesis within active zones for physiological function of neuromuscular endplates and in motoneuron disease.

• DFG Programme: Research Grants