title: Fear-of-intimacy-mediated zinc transport controls the function of zinc-finger transcription factors involved in myogenesis.
abstract: Zinc is a component of one-tenth of all human proteins. Its cellular concentration is tightly regulated because its dyshomeostasis has catastrophic health consequences. Two families of zinc transporters control zinc homeostasis in organisms, but there is little information about their specific developmental roles. We show that the ZIP transporter Fear-of-intimacy (Foi) is necessary for the formation of Drosophila muscles. In foi mutants, myoblasts segregate normally, but their specification is affected, leading to the formation of a misshapen muscle pattern and distorted midgut. The observed phenotypes could be ascribed to the inactivation of specific zinc-finger transcription factors (ZFTFs), supporting the hypothesis that they are a consequence of intracellular depletion of zinc. Accordingly, foi phenotypes can be rescued by mesodermal expression of other ZIP members with similar subcellular localization. We propose that Foi acts mostly as a transporter to regulate zinc intracellular homeostasis, thereby impacting on the activity of ZFTFs that control specific developmental processes. Our results additionally suggest a possible explanation for the presence of large numbers of zinc transporters in organisms based on differences in ion transport specificity and/or degrees of activity among transporters.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC and UAM, C/Nicolás Cabrera 1, Madrid 28049, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Carrasco-Rando
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC and UAM, C/Nicolás Cabrera 1, Madrid 28049, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Atienza-Manuel
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC and UAM, C/Nicolás Cabrera 1, Madrid 28049, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Martín
authors.affiliation: School of Biological Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Burke
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC and UAM, C/Nicolás Cabrera 1, Madrid 28049, Spain mruiz@cbm.csic.es.
authors.forename: Mar
authors.identifier: 0000-0002-9024-1400
authors.initials: M
authors.lastname: Ruiz-Gómez
mesh_terms: D000818:Animals; D001692:Biological Transport; D002459:Cell Fusion; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D009024:Morphogenesis; D024510:Muscle Development; D009154:Mutation / Q000235:genetics; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C478568:foi protein, Drosophila; D015032:Zinc
keywords: Drosophila; Fear-of-intimacy; Mesoderm development; ZIP transporters; Zinc-finger transcription factors