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Journals Genetics Volume 189 Issue 4

The PHR ( P am/ H ighwire/ R PM-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 ( R egulator of P resynaptic M orphology-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. Received May 9, 2011. Accepted September 23, 2011. Copyright © 2011 by the Genetics Society of America Available freely online through the author-supported open access option. « Previous | Next Article » Table of Contents OPEN ACCESS ARTICLE This Article Published online before print October 3, 2011 , doi: 10.1534/genetics.111.134791 Genetics December 1, 2011 vol. 189 no. 4 1297-1307 Free via Open Access: OA » Abstract OA Full Text Full Text (PDF) Classifications Investigations Cellular Genetics Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Tulgren, E. D. PubMed PubMed citation Articles by Tulgren, E. D. Related Content Load related web page information This Months's Issue December 2011, 189 (4) Alert me to new issues of Genetics ABOUT SUBSCRIBE INFO FOR AUTHORS ONLINE SUBMISSION EDITORIAL BOARD CONTACT ALERTS HELP ADVERTISING RSS Help Contact Us International Access Link Print ISSN: 0016-6731 Online ISSN: 1943-2631 Copyright © 2011 by the Genetics Society of America phone: 412-268-1812 fax: 412-268-1813 email: genetics-gsa@andrew.cmu.edu

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PPM-1, a PP2Cα/β phosphatase, Regulates Axon Termination and Synapse Formation in Caenorhabditis elegans

Tulgren, Erik D.; Baker, Scott T.; Rapp, Laramie; Gurney, Allison M.; Grill, Brock
Genetics , Volume 189 (4): 1297
Genetics Society of America – Dec 1, 2011

More Info
  • Publisher Genetics Society of America
  • Copyright Copyright © 2011 by the Genetics Society of America
  • ISSN 0016-6731
  • eISSN 1943-2631
  • D.O.I. 10.1534/genetics.111.134791
  • Publisher site Get PDF  

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