title: Ser¹¹⁹ phosphorylation modulates the activity and conformation of PRRXL1, a homeodomain transcription factor.
abstract: PRRXL1 [paired related homeobox-like 1; also known as DRG11 (dorsal root ganglia 11)] is a paired-like homeodomain transcription factor expressed in DRG and dSC (dorsal spinal cord) nociceptive neurons. PRRXL1 is crucial for the establishment and maintenance of nociceptive circuitry, as Prrxl1(-/-) mice present neuronal loss, reduced pain sensitivity and failure to thrive. In the present study, we show that PRRXL1 is highly phosphorylated in vivo, and that its multiple band pattern on electrophoretic analysis is the result of different phosphorylation states. PRRXL1 phosphorylation appears to be differentially regulated along the dSC and DRG development and it is mapped to two functional domains. One region comprises amino acids 107-143, whereas the other one encompasses amino acids 227-263 and displays repressor activity. Using an immunoprecipitation-MS approach, two phosphorylation sites were identified, Ser¹¹⁹ and Ser²³⁸. Phosphorylation at Ser¹¹⁹ is shown to be determinant for PRRXL1 conformation and transcriptional activity. Ser¹¹⁹ phosphorylation is thus proposed as a mechanism for regulating PRRXL1 function and conformation during nociceptive system development.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Soares-dos-Reis
authors.forename: Ana S
authors.initials: AS
authors.lastname: Pessoa
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Matos
authors.forename: Miguel
authors.initials: M
authors.lastname: Falcão
authors.affiliation: ‡Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Mendes
authors.affiliation: ‡Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Manadas
authors.forename: Filipe A
authors.initials: FA
authors.lastname: Monteiro
authors.forename: Deolinda
authors.initials: D
authors.lastname: Lima
authors.forename: Carlos
authors.initials: C
authors.lastname: Reguenga
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002460:Cell Line; D047108:Embryonic Development; D005260:Female; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D009619:Nociceptors / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C433766:Prrxl1 protein, mouse; D011994:Recombinant Proteins; C483497:Rgmb protein, mouse; D014157:Transcription Factors; D012694:Serine