Disease relevance of ctp

• Interactions between TcTex-1 and a diverse set of proteins such as the dynein intermediate chain, Fyn, DOC2, FIP1, the poliovirus receptor, CD155, and the rhodopsin cytoplasmic tail have been reported; yet, despite the broad range of targets, a consensus binding sequence remains uncertain [1].
• Wolbachia utilizes host microtubules and Dynein for anterior localization in the Drosophila oocyte [2].
• Consequently, the complete lack of the outer dynein arms in Threads- males most probably causes sperm immotility and hence infertility of the fly [3].

High impact information on ctp

• The molecular motor dynein is involved in targeting swallow and bicoid RNA to the anterior pole of Drosophila oocytes [4].
• We identify dynein light chain-1 (Ddlc-1), a component of the minus-end-directed microtubule motor cytoplasmic dynein, as a Swa-binding protein [4].
• Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster [5].
• The ddlc1 gene maps to 4E1-2 and encodes an 89-amino-acid polypeptide with a high similarity to the axonemal 8-kDa outer-arm dynein light chain from Chlamydomonas flagella [5].
• The structure is homodimeric with a domain swapping of beta-strand 2 and has a fold similar to the dynein light chain, LC8 [1].

Biological context of ctp

• We have overexpressed LC8 from Drosophila melanogaster and characterized its dimerization and folding using analytical ultracentrifugation, size-exclusion chromatography, circular dichroism, and fluorescence spectroscopy [6].
• Constructs of IC74, IC(1-143), and IC(30-143) that include the LC8 binding site but with and without the first 30 residues were prepared, and their binding and protection patterns were compared to our previous results for IC(1-289) [7].
• An interaction between LC8 and the Drosophila protein swallow has been previously characterized and supports a role for dynein in the localization of maternal morphogens during oogenesis [8].
• The dpp2c1 gene maps to 4E1-2 on the X chromosome, 1.5 kb upstream of the ddlc1 gene [9].
• LC8c differed from the other two human LC8 sequences in that it has amino acid substitutions in the intermediate chain binding domain at the C-terminal of the molecule [10].

Anatomical context of ctp

• A quantitative assay showed that average number of elongation cones was reduced, they were increasingly deformed, and average cyst lengths were shortened in ddlc1 hemizygous testes [11].

Associations of ctp with chemical compounds

• The observation that dimeric LC8 dissociates at low pH can be explained by titration of a histidine pair in the dimer interface [6].
• Ciona outer arm dynein contains six light chains (LC) including a leucine-rich repeat protein, Tctex1- and Tctex2-related proteins, a protein similar to Drosophila roadblock and two components related to Chlamydomonas LC8 [12].

Physical interactions of ctp

• We propose that Swa acts as an adaptor for the dynein complex and thereby enables dynein to transport bcd RNA along microtubules to their minus ends at the anterior pole of the oocyte [4].

Regulatory relationships of ctp

• Dynein light chain 1 regulates dynamin-mediated F-actin assembly during sperm individualization in Drosophila [13].

Other interactions of ctp

• Upon addition of LC8, N-IC74 undergoes a significant conformational change from largely unfolded to a more ordered structure [14].
• 8. Far-UV CD and fluorescence spectra demonstrate that pH-dissociated LC8 retains native secondary and tertiary structures, while the diminished near-UV CD signal shows loss of quaternary structure [6].
• The deduced amino acid sequence of its open reading frame exhibits high homology to members of the recently discovered roadblock/LC7 protein family (robl/LC7) of dynein-associated proteins [15].

Analytical, diagnostic and therapeutic context of ctp

• Developmental Northern (RNA) blot analysis and ovary and embryo RNA in situ hybridizations indicate that the ddlc1 gene is expressed ubiquitously [5].
• The interactions of LC8 from Drosophila melanogaster with constructs of IC74 were characterized in vitro by affinity methods, limited proteolysis, and circular dichroism spectroscopy [7].
• Sequence analysis of a approximately 400 amino acid region encompassing the putative hydrolytic ATP-binding site shows that the dynein genes fall into at least six distinct classes [16].

References