title: Mutations in the Drosophila orthologs of the F-actin capping protein alpha- and beta-subunits cause actin accumulation and subsequent retinal degeneration.
abstract: The progression of several human neurodegenerative diseases is characterized by the appearance of intracellular inclusions or cytoskeletal abnormalities. An important question is whether these abnormalities actually contribute to the degenerative process or whether they are merely manifestations of cells that are already destined for degeneration. We have conducted a large screen in Drosophila for mutations that alter the growth or differentiation of cells during eye development. We have used mitotic recombination to generate patches of homozygous mutant cells. In our entire screen, mutations in only two different loci, burned (bnd) and scorched (scrd), resulted in eyes in which the mutant patches appeared black and the mutant tissue appeared to have undergone degeneration. In larval imaginal discs, growth and cell fate specification occur normally in mutant cells, but there is an accumulation of F-actin. Mutant cells degenerate much later during the pupal phase of development. burned mutations are allelic to mutations in the previously described cpb locus that encodes the beta-subunit of the F-actin capping protein, while scorched mutations disrupt the gene encoding its alpha-subunit (cpa). The alpha/beta-heterodimer caps the barbed ends of an actin filament and restricts its growth. In its absence, cells progressively accumulate actin filaments and eventually die. A possible role for their human orthologs in neurodegenerative disease merits further investigation.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Delalle
authors.forename: Cathie M
authors.initials: CM
authors.lastname: Pfleger
authors.forename: Eugene
authors.initials: E
authors.lastname: Buff
authors.forename: Paula
authors.initials: P
authors.lastname: Lueras
authors.forename: Iswar K
authors.initials: IK
authors.lastname: Hariharan
mesh_terms: D051344:Actin Capping Proteins / Q000235:genetics*; D051339:Actin Depolymerizing Factors / Q000235:genetics; D000199:Actins / Q000378:metabolism*; D000818:Animals; D004330:Drosophila / Q000235:genetics*; D005820:Genetic Testing; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics*; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000648:ultrastructure*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology
chemical_list: D051344:Actin Capping Proteins; D051339:Actin Depolymerizing Factors; D000199:Actins