title: The Seckel syndrome and centrosomal protein Ninein localizes asymmetrically to stem cell centrosomes but is not required for normal development, behavior, or DNA damage response in Drosophila.
abstract: Ninein (Nin) is a centrosomal protein whose gene is mutated in Seckel syndrome (SCKL, MIM 210600), an inherited recessive disease that results in primordial dwarfism, cognitive deficiencies, and increased sensitivity to genotoxic stress. Nin regulates neural stem cell self-renewal, interkinetic nuclear migration, and microtubule assembly in mammals. Nin is evolutionarily conserved, yet its role in cell division and development has not been investigated in a model organism. Here we characterize the single Nin orthologue in Drosophila Drosophila Nin localizes to the periphery of the centrosome but not at centriolar structures as in mammals. However, Nin shares the property of its mammalian orthologue of promoting microtubule assembly. In neural and germline stem cells, Nin localizes asymmetrically to the younger (daughter) centrosome, yet it is not required for the asymmetric division of stem cells. In wing epithelia and muscle, Nin localizes to noncentrosomal microtubule-organizing centers. Surprisingly, loss of nin expression from a nin mutant does not significantly affect embryonic and brain development, fertility, or locomotor performance of mutant flies or their survival upon exposure to DNA-damaging agents. Although it is not essential, our data suggest that Nin plays a supportive role in centrosomal and extracentrosomal microtubule organization and asymmetric stem cell division.
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, M5G 0A4, Canada Cell Biology Program, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.
authors.forename: Vito
authors.initials: V
authors.lastname: Mennella
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300.
authors.forename: Steven
authors.initials: S
authors.lastname: Marks
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
authors.forename: Jill
authors.initials: J
authors.lastname: Wildonger
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, M5G 0A4, Canada Cell Biology Program, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.
authors.forename: Esraa
authors.initials: E
authors.lastname: Elnagdi
authors.affiliation: The Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-2240.
authors.forename: David
authors.initials: D
authors.lastname: Agard
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300 Timothy.megraw@med.fsu.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Megraw
mesh_terms: D000818:Animals; D002455:Cell Division; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004249:DNA Damage; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: C051924:Bsg25D protein, Drosophila; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins