Disease relevance of Gl

• We used the P[Gal4] insertion strains to target expression of tetanus toxin light chain to these sensory neurons in wild-type animals and showed that this blocked the resistance reflex and produced a phenocopy of the Glued result [1].

High impact information on Gl

• Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued [2].
• The Glued mutation is dominant, with pleiotropic developmental defects in heterozygotes and an embryonic lethal phenotype in homozygotes [3].
• Consistent with this notion, we find that blocking retrograde axonal transport by overexpression of dominant-negative p150/Glued in neurons inhibits BMP signaling in motoneurons [4].
• An RNAi-based screen to identify the molecular mechanisms that regulate synapse retraction identified Arp-1/centractin, a subunit of the dynactin complex [5].
• The Glued protein is enriched within the presynaptic nerve terminal, and presynaptic expression of a dominant-negative Glued transgene enhances retraction [5].

Biological context of Gl

• In genetic complementation studies, we find that certain mutations in the cytoplasmic dynein heavy chain gene Dhc64C act as dominant suppressors or enhancers of the rough eye phenotype of the dominant Glued mutation [6].
• The spatial and temporal distribution of the Glued complex during oogenesis is shown by immunocytochemistry methods to be identical to the pattern previously described for cytoplasmic dynein [6].
• The Drosophila Glued gene product shares sequence homology with the p150 component of vertebrate dynactin [6].
• We evaluated the functions of the dynein-dynactin complex by using RNA interference (RNAi)-mediated depletion of distinct subunits in Drosophila S2 cells [7].
• ZW10 helps recruit dynactin and dynein to the kinetochore [8].

Anatomical context of Gl

• In our analysis of the Glued polypeptides encoded by the dominant mutation, Glued, we identify a truncated polypeptide that fails to assemble into the wild-type 20S complex, but retains the ability to copurify with microtubules [6].
• Taken together, these results suggest that the extension and assembly of AJs as well as determination of the rhabdomere domain in photoreceptor development are Gl dependent [9].
• There are striking sequence and conformation similarities between the Glued alpha-helical domains and those found in certain filamentous proteins from various organisms, particularly in muscle fibers and intermediate filaments [10].
• An affinity column with covalently bound Glued protein retained cytoplasmic dynein from S-2 cytosol [11].
• The mechanism by which dynactin facilitates cytoplasmic dynein-dependent vesicle transport is unknown [12].

Associations of Gl with chemical compounds

• However, when this Ser was changed to Asp or Glu, transformation and transcriptional repression by v-Rel were significantly inhibited and c-Rel showed a diffuse nuclear and cytoplasmic localization in CEF [13].
• Immunoblotting of sucrose gradient-fractionated brain cytosol revealed p150Glued, p50, and centractin to cosediment exclusively at 20 S. Immunofluorescence microscopy using antibody to p150Glued revealed centrosomal staining, which was abolished by microtubule depolymerization [14].
• Another class of lethal Glued mutations was induced in the normal Gl+ strain by ethyl methanesulfonate (EMS) [15].
• Both Gln and Glu mutant proteins can form a clamp complex in the presence of 5'-adenylyl-beta,gamma-imidodiphosphate, albeit with a lower efficiency than the wild-type enzyme [16].
• The mutation of Arg(414) to Leu and Glu resulted in the total loss of NO formation activity and of the heme reduction with NADPH [17].

Regulatory relationships of Gl

• Dynactin is a multiprotein complex that stimulates cytoplasmic dynein-mediated vesicle motility in vitro [6].

Other interactions of Gl

• Furthermore, we show that a mutation that was previously isolated as a suppressor of the Glued mutation is an allele of Dhc64C [6].
• Regulation of cytoplasmic dynein function in vivo by the Drosophila Glued complex [6].
• Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex [18].
• Glycogen synthase kinase-3beta phosphorylated peptides with Ser(P) and Thr(P) in the priming position, but peptides with Tyr(P), Thr, Glu or Asp were not phosphorylated [19].

Analytical, diagnostic and therapeutic context of Gl

• Sequence analysis of the complete cDNA and encoded polypeptide for the Glued gene of Drosophila melanogaster [10].
• Immunoprecipitations from S-2 cytosol with the anti-Glued antibody resulted in the co-precipitation of subunits of both cytoplasmic dynein and the dynactin complex [11].
• Therefore, the distributions observed via in situ hybridization are consistent with an essential role for p150Glued in retrograde axonal transport [20].
• Nuclear uptake was found to be not only NLS-dependent, but also strongly dependent on the PKA site, whereby substitution of Ser312 by either Ala or Glu using site-directed mutagenesis severely reduced nuclear accumulation [21].
• The polymerase chain reaction was used to amplify six mitochondrial t-RNAs for Ala, Arg, Asn, Ser, Glu and Phe between genes for mitochondrial NADH dehydrogenases 3 and 5 [22].

References