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Abstract

Neurons communicate through synapses, where neurotransmitters released from the presynaptic terminal bind to receptors on the postsynaptic terminal. Synaptic exocytosis requires multiple highly conserved proteins localized at a specialized area in the presynaptic terminal. The Mizumoto lab found that unc-43, a single ortholog of Calcium-calmodulin-dependent protein kinase II (CaMKII), is required for presynaptic assembly in Caenorhabditis elegans (C. elegans). In mammals, four CaMKII isoforms are encoded by related genes, and mutations in these isoform genes are highly associated with intellectual disabilities (ID). However, the functions of human CaMKII isoforms in the presynaptic assembly are unknown. In this study, I found that CaMKII isoforms have shared and unique roles in presynaptic assembly in C. elegans. At the synaptic level, animals expressing CaMKIIA, CaMKIIB, and CaMKIID showed a wild-type-like presynaptic structure in the DA9 motor neuron. However, CaMKIIB animals are unable to cluster synaptic vesicles (SVs) properly. Additionally, I demonstrated that the ID-associated mutations in CaMKIIA and CaMKIIG caused defects similar to unc-43 mutants. Together, these findings provide insights into the functions of CaMKII isoforms and the pathological impact of ID-associated mutations in CaMKIIA and CaMKIIG on presynaptic assembly.