Disease relevance of ninaC

• In the current report, we demonstrate that the ninaC mutation results in light- and age-dependent retinal degeneration [1].
• The kinase homologous domain (MYOIIIPK) of myosin III was expressed in the baculovirus expression system and purified to homogeneity [2].
• The genome of each of these viruses consists of two segments of double-stranded RNA (molecular weight range between 2.6 x 10(6) and 2.2 x 10(6), and the virion, capsid proteins fall into three size class categories (large, medium, and small; ranging from 100,000 to 27,000) as determined by polyacrylamide slab gel electrophoresis [3].
• There were two instances in which homozygosis for the second chromosome caused sterility in both sexes, which was close to the number expected (2.2) on a random basis of 0.0092 S 0.183 X 131 [4].

High impact information on ninaC

• The Drosophila ninaC locus encodes two photoreceptor cell specific proteins with domains homologous to protein kinases and the myosin heavy chain head [5].
• We show that the ninaC gene, originally isolated as a Drosophila visual mutation with an electrophysiological phenotype, encodes two novel cytoskeletal proteins [5].
• We identified the DNA sequences encoding the ninaC gene by rescuing the electrophysiological phenotype using P-element-mediated germ line transformation [5].
• This calmodulin localization was dependent on the NINAC (neither inactivation nor afterpotential C) unconventional myosins [6].
• Disruption of the NINAC/INAD interaction delayed termination of the photoreceptor response [7].

Biological context of ninaC

• We showed that defects in ninaC resulted in a long-term adaptation phenotype similar to that which occurred in arr2 mutants [8].
• In addition, we found that endocytosis of TRPL-eGFP occurs independently of dynamin, whereas a mutation of the unconventional myosin III, NINAC, hinders complete translocation of TRPL-eGFP to the cell body [9].
• The effects of cAMP were abolished in mutants of the ninaC gene, suggesting this nonconventional myosin as a possible target for PKA-mediated phosphorylation [10].
• This suggests that ninaC has a role in phototransduction and that the retinal degeneration is a secondary effect resulting from the defect in phototransduction [1].
• Distinct roles of the Drosophila ninaC kinase and myosin domains revealed by systematic mutagenesis [11].

Anatomical context of ninaC

• Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC [12].
• Ultrastructural studies show that the polypeptides encoded by ninaC are very likely to be important components of the cytoskeletal structure of rhabdomeral microvilli [13].
• The Drosophila ninaC mutation produces small rhabdomeres with the axial filament of the microvillar cytoskeleton reduced or missing [14].
• Myosin III immunoreactivity in trilobite larvae also revealed the architecture of the central visual pathways associated with the median eye complex and the lateral eyes [15].
• The gamma-tubulin ring complex (gammaTuRC) is a protein complex of relative molecular mass approximately 2.2 x 10(6) that nucleates microtubules at the centrosome [16].

Associations of ninaC with chemical compounds

• To address the requirements for calmodulin binding at each site in vivo, we generated transgenic flies expressing ninaC genes deleted for either C1 or C2 [17].
• The phosphoamino acid analysis revealed that myosin III is a serine/threonine kinase but not a tyrosine kinase [2].
• Double labeling with myosin III and BrdU showed that neurogenesis persists in the larval brain and suggested that new neurons of both the lamina and the medulla originate from a single common proliferation zone [15].
• Polyadenylic acid-containing transcripts of 2.7, 2.2, and 1.7 kilobases (kb) in embryos, pupae, adults, and Kc cells and an additional 1.4-kb transcript in adults were complementary to the Drosophila genomic clones and to v-myc [18].
• Within the 2.2 kb region between hsp23 and gene 1 of the small heat shock gene locus 67B1 of Drosophila melanogaster, an approximately 1 kb perturbation of the chromatin architecture has previously been observed to occur in response to the steroid hormone ecdysone [19].

Physical interactions of ninaC

• Biochemical studies showed that both ninaC proteins bind actin filaments and cosediment with actin filaments in an ATP-sensitive manner [20].

Other interactions of ninaC

• These results outline structural roles for the ninaC proteins, and are consistent with the notion, suggested by their amino acid sequences, that the proteins are actin-based mechanoenzymes [20].
• MYOIIIPK phosphorylated a number of proteins including myosin III p132 and smooth muscle myosin regulatory light chain (LC20), suggesting that myosin III is a multifunctional protein kinase [2].

Analytical, diagnostic and therapeutic context of ninaC

• We have: (1) determined the cellular and subcellular distributions of the ninaC proteins in the Drosophila retina by electron microscopic immunocytochemistry with an antibody specific for epitopes shared by both proteins; (2) characterized the ultrastructure of the mutant phenotype [21].
• The role of p132 and p174 was studied via whole-cell recording and through measurements of the pupil mechanism, i.e. the pigment migration in the photoreceptor cells, in the ninaC mutants, P[ninaC delta 132] (p132 absent), P[ninaC delta 174] (p174 absent), and ninaCP235 (null mutant) [22].
• Two RNAs of 7.4 and 2.2 kb have been identified by Northern blot analysis as the putative eyecolor and segregational products [23].
• To understand structural features of the Drosophila PIMT (dPIMT) important for catalysis, the crystal structure of dPIMT was determined at a resolution of 2.2 A, and site-directed mutagenesis was used to identify the role of Ser-60 in catalysis [24].
• Sequence analysis of the nucleotides spanning the region between 1.3 kb and 2.2 kb revealed a 13-nucleotide motif ACACAAAAAAATA 2059 bp upstream from the start site that duplicated the 'hunchback' binding site, a key site controlling developmental gene expression in Drosophila [25].

References