title: PPM-1, a PP2Cα/β phosphatase, regulates axon termination and synapse formation in Caenorhabditis elegans.
abstract: The PHR (Pam/Highwire/RPM-1) proteins are evolutionarily conserved ubiquitin ligases that regulate axon guidance and synapse formation in Caenorhabditis elegans, Drosophila, zebrafish, and mice. In C. elegans, RPM-1 (Regulator of Presynaptic Morphology-1) functions in synapse formation, axon guidance, axon termination, and postsynaptic GLR-1 trafficking. Acting as an E3 ubiquitin ligase, RPM-1 negatively regulates a MAP kinase pathway that includes: dlk-1, mkk-4, and the p38 MAPK, pmk-3. Here we provide evidence that ppm-1, a serine/threonine phosphatase homologous to human PP2Cα(PPM1A) and PP2Cβ(PPM1B) acts as a second negative regulatory mechanism to control the dlk-1 pathway. We show that ppm-1 functions through its phosphatase activity in a parallel genetic pathway with glo-4 and fsn-1 to regulate both synapse formation in the GABAergic motorneurons and axon termination in the mechanosensory neurons. Our transgenic analysis shows that ppm-1 acts downstream of rpm-1 to negatively regulate the DLK-1 pathway, with PPM-1 most likely acting at the level of pmk-3. Our study provides insight into the negative regulatory mechanisms that control the dlk-1 pathway in neurons and demonstrates a new role for the PP2C/PPM phosphatases as regulators of neuronal development.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Erik D
authors.initials: ED
authors.lastname: Tulgren
authors.forename: Scott T
authors.initials: ST
authors.lastname: Baker
authors.forename: Laramie
authors.initials: L
authors.lastname: Rapp
authors.forename: Allison M
authors.initials: AM
authors.lastname: Gurney
authors.forename: Brock
authors.initials: B
authors.lastname: Grill
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000254:growth & development*; D009474:Neurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D013569:Synapses
chemical_list: D010749:Phosphoprotein Phosphatases