Disease relevance of GSN

• Immunodepletion of Xenopus actin depolymerizing factor (ADF)/cofilin (XAC) from Xenopus egg extracts resulted in Listeria tails that were approximately five times longer than the tails from undepleted extracts [1].
• The ADF restriction resulted in 12 to 25% decrease in body weights at 5 weeks and 5 to 11% decrease in body weights at 18 or 19 weeks [2].

Psychiatry related information on GSN

• Clinically, GSN/1 chickens drooped and had decreased locomotor activity [3].

High impact information on GSN

• To further study this process, we examined ADF expression in chick myocytes cultured in vitro [4].
• We conclude that the ability to regulate ADF activity is important to muscle development since myocytes have both pre- and posttranslational mechanisms for regulating ADF activity [4].
• Four ubiquitous protein kinases failed to phosphorylate ADF in vitro suggesting that ADF phosphorylation in vivo is catalyzed by a more specific kinase [4].
• Its abundance and widespread distribution together with its ability to sequester actin molecules, even those in an already polymerized state, suggest that ADF is a major factor in the regulation of actin filaments in many vertebrate cells [5].
• Adult heart and skeletal muscle are unusual in having very low levels of ADF: less than 0.02% of the soluble protein [5].

Biological context of GSN

• However, responses of the visual evoked potential in GSN/1 chickens were insensitive to xenon flash stimuli [3].
• As an indicator of visual acuity, the spatial frequency characteristics of GSN/1 chickens showed poor scores at high frequency [3].
• Slow axonal transport of soluble actin with actin depolymerizing factor, cofilin, and profilin suggests actin moves in an unassembled form [6].
• Addition of ADF to monomeric actin inhibits actin assembly as well as the ATP hydrolysis that normally accompanies assembly [7].
• Chick actin depolymerizing factor (ADF) is an actin binding protein previously shown to rapidly depolymerize actin filaments in vitro, yielding a 1:1 complex of ADF and actin monomer [7].

Anatomical context of GSN

• Visual pathways of a new mutant of chicken (GSN/1) with hereditary visual impairment were ophthalmologically, electrophysiologically, and histopathologically examined [3].
• Histologically, the retina of GSN/1 chickens was slightly hypoplastic and the retinal ganglion cells decreased in number, although there were no degenerative or reactive changes [3].
• No proteins are specifically recognized by the ADF antiserum in extracts from Acanthamoeba castellanii or from nerve tissue of several invertebrates [5].
• Indirect immunofluorescence shows that ADF is present throughout the cytosol of most cells and at the leading edge of ruffled membranes and in the neuronal growth cone [5].
• Brain tissue and cultured cell lines from several other vertebrates, including mammals, all possess proteins of identical size to ADF that are recognized by the ADF antiserum [5].

Associations of GSN with chemical compounds

• Brain ADF migrates as a single polypeptide of 19,000 kDa on SDS-containing polyacrylamide gels [8].
• All six cysteine residues could be chemically modified with eosinylmaleimide under nondenaturing conditions; however, ADF activity was lost when more than one cysteine residue was modified [8].
• Here we show that ADF protects actin monomer from denaturation by EDTA by inhibiting the exchange of actin-bound nucleotide [7].
• ADF microheterogeneity has been observed upon nonequilibrium pH gradient electrophoresis in polyacrylamide gels containing 9 M urea, the major isoform having a pI of congruent to 7.9-8 [8].
• Plasma uric acid and hepatic glutamic pyruvic transaminase were affected, but not consistently, by ADF [2].

Analytical, diagnostic and therapeutic context of GSN

• We have purified both ADF isoforms from myocytes and have shown by peptide mapping and partial sequence analysis that the new isoform is structurally related to ADF [4].
• 0. ADF can interact with either monomeric or filamentous actin to give a complex which can be isolated by gel filtration chromatography [8].
• Quantitative immunoblotting with a monospecific antibody to ADF indicated that ADF comprises 0.3% of the total brain protein, resulting in an actual purification yield of about 20% [8].

References