Developmental control of synaptogenesis of the Caenorhabditis elegans egg-laying motor neuron. During early post-embryonic development, two synaptic structures are assembled at the SSR and PSR. The Cullin-1 E3 ligase is present at both sites, but is active only at the SSR where it degrades synaptic proteins. The function of Cullin E3 is inhibited at the PSR by SYG-1, thereby preventing the binding of the F-box protein SEL-10 to the Cullin complex. This spatial control of SCF complex formation leads to the elimination of the SSR, while maintaining the PSR during adulthood. E2, E2 ligase; PSR, primary synapse region; RBX, Ring box molecule; SCF, Skip1, Cullin, F-box; SEL-10, suppressor/enhancer of LIN-12; Skip1, S-phase kinase-associated protein 1; SKR-1, Skip1-related ubiquitin ligase complex component; SSR, secondary synapse region; SYG-1, synaptogenesis abnormal.

Thorsten Hoppe

Multimeric cullin-based E3 ligases control neuronal development and activity. Cullin complexes direct protein turnover in the presynaptic and postsynaptic compartments. A Cullin-1 complex containing the F-box molecule FSN-1 (Caenorhabditis elegans)/DFsn (Drosophila) and the RING-finger protein RPM-1 (C. elegans)/Highwire (Drosophila) degrades DLK-1 (C. elegans)/Wallenda (Drosophila) at the presynaptic compartment to control synaptogenesis. In C. elegans, RPM-1 also functions in an FSN-1-independent pathway during axon termination. In this case, it interacts with the guanine nucleotide-exchange factor GLO-4 independently of its RING-finger domain and promotes vesicular trafficking through a Rab GTPase pathway. The F-box protein Scrapper forms a cullin-based complex to degrade the vesicle-priming factor RIM1, thereby controlling vesicle release from the presynaptic side. At the postsynaptic compartment, a Cullin-1 complex including the F-box protein LIN-23 influences the recycling of the AMPA-type receptor GLR-1. The stability of GLR-1 itself is also regulated by the Cullin-3 complex through its substrate-recognition factor KEL-8. AMPA, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; DFsn, Drosophila homologue of FSN-1; DLK-1, death associated protein kinase-like kinase 1; E2, E2 ligase; FSN-1, F-box synaptic protein 1; GLO-4, gut granule loss 4; GLR-1, glutamate receptor family 1; KEL-8, Kelch repeat-containing protein 8; LIN-23, abnormal cell lineage 23; Rab, Ras-related in brain; RBX, Ring box molecule; RIM1, regulating synaptic membrane exocytosis 1; RING, really interesting new gene; RPM-1, regulator of presynaptic morphology 1; Skip1, S-phase kinase-associated protein 1; SKR-1, Skip1-related ubiquitin ligase complex component.

Alexandra Segref