Mutations in the Novel Membrane Protein Spinster Interfere with Programmed Cell Death and Cause Neural Degeneration inDrosophila melanogaster
Abstract
Mutations in the Novel Membrane Protein Spinster Interfere with Programmed Cell Death and Cause Neural Degeneration in Drosophila melanogaster Yoshiro Nakano 1 , 2 , 3 , † , Kazuko Fujitani 1 , 3 , Joyce Kurihara 2 , Janet Ragan 2 , Kazue Usui-Aoki 4 , Lori Shimoda 2 , Tamas Lukacsovich 1 , Keiko Suzuki 3 , 5 , Mariko Sezaki 3 , Yumiko Sano 3 , Ryu Ueda 3 , Wakae Awano 1 , Mizuho Kaneda 6 , Masato Umeda 6 , and Daisuke Yamamoto 1 , 3 , 4 , * ERATO Yamamoto Behavior Genes Project, Japan Science and Technology Corporation at Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194-8511, 1 Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194-8511, 3 Waseda University, School of Human Sciences and Advanced Research Institute for Science and Engineering, Tokorozawa, Saitama 359-1192, 4 Laboratory of Entomology, Tamagawa University, Machida, Tokyo 194-8610, 5 and The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, 6 Japan, and ERATO Yamamoto Behavior Genes Project, Japan Science and Technology Corporation at the Center for Conservation Biology Research and Training, University of Hawaii at Manoa, Honolulu, Hawaii 96822 2 ABSTRACT Mutations in the spin gene are characterized by an extraordinarily strong rejection behavior of female flies in response to male courtship. They are also accompanied by decreases in the viability, adult life span, and oviposition rate of the flies. In spin mutants, some oocytes and adult neural cells undergo degeneration, which is preceded by reductions in programmed cell death of nurse cells in ovaries and of neurons in the pupal nervous system, respectively. The central nervous system (CNS) of spin mutant flies accumulates autofluorescent lipopigments with characteristics similar to those of lipofuscin. The spin locus generates at least five different transcripts, with only two of these being able to rescue the spin behavioral phenotype; each encodes a protein with multiple membrane-spanning domains that are expressed in both the surface glial cells in the CNS and the follicle cells in the ovaries. Orthologs of the spin gene have also been identified in a number of species from nematodes to humans. Analysis of the spin mutant will give us new insights into neurodegenerative diseases and aging.