title: ABCC5 is required for cAMP-mediated hindgut invagination in sea urchin embryos.
abstract: ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse substrates across membranes. Many are known to efflux signaling molecules and are extensively expressed during development. However, the role of transporters in moving extracellular signals that regulate embryogenesis is largely unexplored. Here, we show that a mesodermal ABCC (MRP) transporter is necessary for endodermal gut morphogenesis in sea urchin embryos. This transporter, Sp-ABCC5a (C5a), is expressed in pigment cells and their precursors, which are a subset of the non-skeletogenic mesoderm (NSM) cells. C5a expression depends on Delta/Notch signaling from skeletogenic mesoderm and is downstream of Gcm in the aboral NSM gene regulatory network. Long-term imaging of development reveals that C5a knockdown embryos gastrulate, but ∼90% develop a prolapse of the hindgut by the late prism stage (∼8 h after C5a protein expression normally peaks). Since C5a orthologs efflux cyclic nucleotides, and cAMP-dependent protein kinase (Sp-CAPK/PKA) is expressed in pigment cells, we examined whether C5a could be involved in gastrulation through cAMP transport. Consistent with this hypothesis, membrane-permeable pCPT-cAMP rescues the prolapse phenotype in C5a knockdown embryos, and causes archenteron hyper-invagination in control embryos. In addition, the cAMP-producing enzyme soluble adenylyl cyclase (sAC) is expressed in pigment cells, and its inhibition impairs gastrulation. Together, our data support a model in which C5a transports sAC-derived cAMP from pigment cells to control late invagination of the hindgut. Little is known about the ancestral functions of ABCC5/MRP5 transporters, and this study reveals a novel role for these proteins in mesoderm-endoderm signaling during embryogenesis.
authors.affiliation: Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0202, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Shipp
authors.affiliation: Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0202, USA.
authors.forename: Rose Z
authors.initials: RZ
authors.lastname: Hill
authors.affiliation: Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0202, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Moy
authors.affiliation: Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0202, USA.
authors.forename: Tufan
authors.initials: T
authors.lastname: Gökırmak
authors.affiliation: Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0202, USA hamdoun@ucsd.edu.
authors.forename: Amro
authors.initials: A
authors.lastname: Hamdoun
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001896:Boron Compounds / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism; D005775:Gastrula / Q000378:metabolism; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D017404:In Situ Hybridization, Fluorescence; D007422:Intestines / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009024:Morphogenesis; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009711:Nucleotides / Q000737:chemistry; D010641:Phenotype; D010858:Pigmentation; D012617:Sea Urchins / Q000196:embryology*; D015398:Signal Transduction
chemical_list: D000262:Adenylyl Cyclases; D001896:Boron Compounds; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009711:Nucleotides; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
keywords: ABC transporter; ABCC5; Developmental signaling; Gastrulation; MRP5; Sea urchin; Soluble adenylyl cyclase (sAC); cAMP