title: The MAP kinase pathway coordinates crossover designation with disassembly of synaptonemal complex proteins during meiosis.
abstract: Asymmetric disassembly of the synaptonemal complex (SC) is crucial for proper meiotic chromosome segregation. However, the signaling mechanisms that directly regulate this process are poorly understood. Here we show that the mammalian Rho GEF homolog, ECT-2, functions through the conserved RAS/ERK MAP kinase signaling pathway in the C. elegans germline to regulate the disassembly of SC proteins. We find that SYP-2, a SC central region component, is a potential target for MPK-1-mediated phosphorylation and that constitutively phosphorylated SYP-2 impairs the disassembly of SC proteins from chromosomal domains referred to as the long arms of the bivalents. Inactivation of MAP kinase at late pachytene is critical for timely disassembly of the SC proteins from the long arms, and is dependent on the crossover (CO) promoting factors ZHP-3/RNF212/Zip3 and COSA-1/CNTD1. We propose that the conserved MAP kinase pathway coordinates CO designation with the disassembly of SC proteins to ensure accurate chromosome segregation.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.
authors.forename: Saravanapriah
authors.initials: S
authors.lastname: Nadarajan
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Firaz
authors.initials: F
authors.lastname: Mohideen
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.
authors.forename: Yonatan B
authors.initials: YB
authors.lastname: Tzur
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Nuria
authors.initials: N
authors.lastname: Ferrandiz
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Oliver
authors.identifier: http://orcid.org/0000-0002-5054-0051
authors.initials: O
authors.lastname: Crawley
authors.affiliation: Proteomics facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Montoya
authors.affiliation: Proteomics facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Faull
authors.affiliation: Proteomics facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: Proteomics facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Pedro R
authors.identifier: http://orcid.org/0000-0002-3426-2274
authors.initials: PR
authors.lastname: Cutillas
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Jambhekar
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Blower
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Enrique
authors.initials: E
authors.lastname: Martinez-Perez
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: J Wade
authors.initials: JW
authors.lastname: Harper
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.
authors.forename: Monica P
authors.initials: MP
authors.lastname: Colaiacovo
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002460:Cell Line; D020090:Chromosome Segregation; D003434:Crossing Over, Genetic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008540:Meiosis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013573:Synaptonemal Complex / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C507872:Ect-2 protein, C elegans; D020662:Guanine Nucleotide Exchange Factors; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans
keywords: <i>c. elegans</i>; MAP kinase; SYP-2; cell biology; chromosomes; crossover recombination; genes; germline; meiosis; synaptonemal complex