rpm-1, A Conserved Neuronal Gene that Regulates Targeting and Synaptogenesis in C. elegans

Abstract

Little is known of mechanisms regulating presynaptic differentiation. We identified rpm-1 in a screen for mutants with defects in patterning of a presynaptic marker at certain interneuronal synapses. The predicted RPM-1 protein contains zinc binding, RCC1, and other conserved motifs. In rpm-1 mutants, mechanosensory neurons fail to accumulate tagged vesicles, retract synaptic branches, and ectopically extend axons. Some motor neurons branch and overgrow; others show altered synaptic organization. Expression of RPM-1 in the presynaptic mechanosensory neurons is sufficient to rescue phenotypes in these cells. Certain rpm-1 phenotypes are temperature sensitive, revealing that RPM-1 function can be bypassed by maintaining mutants at the permissive temperature at stages commensurate with synapse formation in wild-type animals. These results indicate that RPM-1 functions cell autonomously during synaptogenesis to regulate neuronal morphology.

Rabphilin Potentiates SolubleN-Ethylmaleimide Sensitive Factor Attachment Protein Receptor Function Independently of rab3

“…2-methyl-2- [methylthio]proprionaldehyde O- [methylcarbamoyl]oxime (aldicarb) was obtained from Chem Services, Inc. (West Chester, PA). Pharyngeal pumping and aldicarb sensitivity were tested as described previously , and snt-1(md290) represent null alleles based on molecular, genetic, and immunohistochemical criteria (Nonet et al, 1993Schaefer et al, 2000). ae x -3( y255) behaves as a strong loss-of-f unction allele (Iwasaki et al, 1997).…”

GABA Is Dispensable for the Formation of Junctional GABA Receptor Clusters inCaenorhabditis elegans

“…Interestingly, proteins of the presynaptic active zone are properly localized in unc-104 mutants. Specifically, liprin/ SYD-2 (Zhen and Jin, 1999), Rab-3 interacting molecule/ UNC-10 ( Koushika et al, 2001), and RPM-1 (Schaefer et al, 2000;Zhen et al, 2000) are correctly localized in the dorsal cord; however, these incomplete synapses cannot direct the clustering of GABA receptors. Therefore, sites of presynaptic differentiation can be specified in the motor neuron independently from the formation of synaptic vesicle aggregates.…”

Identification of a Peptide Inhibitor of the RPM-1·FSN-1 Ubiquitin Ligase Complex

“…Synapse Formation-Previous studies have shown that rpm-1, fsn-1, and glo-4 loss-of-function (lf) mutants have defects in axon termination and synapse formation in the mechanosensory neurons of C. elegans (3,12). Furthermore, fsn-1 and glo-4 function in parallel genetic pathways to mediate the function of rpm-1 (12).…”

“…Studies in worms, flies, fish, and mice have identified roles for the PHR proteins in synapse formation (2)(3)(4)(5), axon guidance and extension (6 -11), and axon termination (3,(12)(13)(14).…”