Synaptogenesis entails the development and establishment of functional synapses, which form the fundamental unit of communication in the nervous system. Initially identified in Caenorhabditis elegans (C. elegans), the FSN-1, F-box protein family has emerged as evolutionarily conserved binding partners of PHR family proteins, which regulate synaptogenesis. Previously, we have shown that FSN-1 and RPM-1 form a SCF/FSN-1/RPM-1 ubiquitin ligase complex that negatively regulates synapse growth by downregulating presynaptic targets, like the MAP kinase pathway. For my master’s thesis, I used a combination of both candidate and forward genetic approaches to identify additional components of signaling pathways that are regulated by FSN-1 during synaptogenesis. Our studies are among the first to suggest diverging roles for these partners and provide the first evidence for a mechanism through which the F-box protein regulates synaptogenesis via retrograde insulin/IGF/FOXO signaling and glucosaminidase/O-GlcNAc modifications.

Synaptogenesis entails the development and establishment of functional synapses, which form the fundamental unit of communication in the nervous system. Initially identified in Caenorhabditis elegans (C. elegans), the FSN-1, F-box protein family has emerged as evolutionarily conserved binding partners of PHR family proteins, which regulate synaptogenesis. Previously, we have shown that FSN-1 and RPM-1 form a SCF/FSN-1/RPM-1 ubiquitin ligase complex that negatively regulates synapse growth by downregulating presynaptic targets, like the MAP kinase pathway. For my master’s thesis, I used a combination of both candidate and forward genetic approaches to identify additional components of signaling pathways that are regulated by FSN-1 during synaptogenesis. Our studies are among the first to suggest diverging roles for these partners and provide the first evidence for a mechanism through which the F-box protein regulates synaptogenesis via retrograde insulin/IGF/FOXO signaling and glucosaminidase/O-GlcNAc modifications.

Synapses are specialized sub-cellular junctions that transmit signals between neurons and their targets. In Caenorhabditis elegans (C. elegans) the F-box protein FSN-1 and the PHR family member RPM-1 form the SCFFSN-1 E3 ubiquitin ligase, which plays an important role in regulating synaptic growth factors. This SCF complex is evolutionarily conserved across species, and regulates many cellular processes including axon outgrowth, apoptosis and synaptogenesis. This thesis focuses on identifying targets of SCFFSN-1 that contribute to synaptogenesis. Forward genetics was employed to screens and isolate mutants that exhibit genetic interactions with fsn-1. I have identified an allele of the MAPK pmk-3(hp246) and three alleles of the MAPKKK dlk-1(hp180, hp192, hp195) that suppress fsn-1 defects. In addition, I have isolated five fsn-1 suppressing alleles and evidence suggests that these suppressors are likely novel fsn-1 suppressors.

Synapses are specialized sub-cellular junctions that transmit signals between neurons and their targets. In Caenorhabditis elegans (C. elegans) the F-box protein FSN-1 and the PHR family member RPM-1 form the SCFFSN-1 E3 ubiquitin ligase, which plays an important role in regulating synaptic growth factors. This SCF complex is evolutionarily conserved across species, and regulates many cellular processes including axon outgrowth, apoptosis and synaptogenesis. This thesis focuses on identifying targets of SCFFSN-1 that contribute to synaptogenesis. Forward genetics was employed to screens and isolate mutants that exhibit genetic interactions with fsn-1. I have identified an allele of the MAPK pmk-3(hp246) and three alleles of the MAPKKK dlk-1(hp180, hp192, hp195) that suppress fsn-1 defects. In addition, I have isolated five fsn-1 suppressing alleles and evidence suggests that these suppressors are likely novel fsn-1 suppressors.