Disease relevance of Act42A

• Actin dynamics is recognized as being a determinant in many developmental processes and pathologies, such as cell polarity, morphogenesis and tumour metastasis [1].
• Mutations in Drosophila filamin disrupt actin filament organization and compromise membrane integrity during oocyte development, resulting in female sterility [2].
• The behavior of modular actin cytoskeletons has implications for other actin-based cytoskeletal systems, e.g., those involved in Listeria movement, in cell spreading, and in retrograde flow in growth cones and fibroblasts [3].
• We demonstrated that these two recombinant phages, hybridizing preferentially with poly(A)+ RNA of ecdysterone-treated cells, contain the 5 C actin gene [4].
• Salmonella enterica SpvB ADP-ribosylates actin at position arginine-177-characterization of the catalytic domain within the SpvB protein and a comparison to binary clostridial actin-ADP-ribosylating toxins [5].

Psychiatry related information on Act42A

• The Drosophila fragile X mental retardation protein controls actin dynamics by directly regulating profilin in the brain [6].

High impact information on Act42A

• We show that these proteins govern apical actin assembly and thus control the orientation, but not assembly, of ciliary microtubules [7].
• However, DmIKK epsilon-mediated degradation of DIAP1 does not regulate apoptosis as might be predicted but instead regulates actin dynamics, cell morphology, and the differentiation of sensory organ precursor cells [8].
• Upon LKB1 activation, single cells rapidly remodel their actin cytoskeleton to form an apical brush border [9].
• The region that shows the strongest interaction with actin is an amphipathic N-terminal alpha helix, present in all beta-thymosin/WH2 domains, which recognizes the ATP bound actin structure and uses the shear motion of actin linked to ATP hydrolysis to control polymerization [10].
• Crystallographic ((1)H, (15)N), NMR, and mutagenetic data reveal that the weaker interaction of the C-terminal region of beta-thymosin/WH2 domain with actin accounts for the switch in function from inhibition to promotion of actin assembly [10].

Chemical compound and disease context of Act42A

• These results are consistent with the fact that human Merlin is encoded by the gene for the tumour suppressor neurofibromatosis-2 and is a member of the Ezrin-Radixin-Moesin family of proteins that link actin to transmembrane proteins [11].

Biological context of Act42A

• A hybrid transgene containing the protein coding sequence for the Act42A isoform, under the control of the regulatory regions of the Act5C gene, also rescues the lethality of the Act5C mutants [12].
• Most organisms have multiple cytoplasmic actin genes that encode isoforms with slightly different amino acid sequences [12].
• These results suggest the amino acid differences between these two cytoplasmic actin isoforms are not important for function and the need for increased gene dosage to provide more actin is not likely to explain the existence of multiple genes [12].
• To date, only a single actin binding protein (TropomyosinII) has been identified with a putative role in osk mRNA and protein anchoring [13].
• Many eukaryotic genomes encode multiple actin protein isoforms that differ from each other by only a few residues [14].

Anatomical context of Act42A

• However, how actin interacts with the plasma membrane is poorly understood [1].
• When moesin function is reduced in the female germ-line, defects in cortical actin organization are also observed [15].
• In addition, both mutant oocytes and mutant escaper adults have abnormalities in the organization of the actin cytoskeleton [16].
• MOESIN crosslinks actin and cell membrane in Drosophila oocytes and is required for OSKAR anchoring [13].
• The most striking difference was observed within the Z-lines of the sarcomeres: one actin was specifically excluded and we mapped this feature to one or both of two residues within the C-terminal half of the protein [14].

Associations of Act42A with chemical compounds

• The cDNA encoding the entire RVGP gene was cloned in an expression plasmid under the control of the constitutive actin promoter (Ac), which was co-transfected into S2 cells together with a hygromycin selection plasmid [17].
• One of the Drosophila actin genes, DmA4, is split within a glycine codon at position 13; none of the remaining five genes is interrupted in the analogous position [18].
• Surprisingly, in each of these derived actin amino acid sequences in the initiator methionine is directly followed by a cysteine residue, which in turn precedes the string of three acidic amino acids characteristic of the amino termini of mature vertebrate cytoplasmic actins [18].
• 20-Hydroxyecdysone regulates cytoplasmic actin gene expression in Drosophila cultured cells [19].
• Although many proteins in this family are thought to act by linking the actin-based cytoskeleton to transmembrane proteins, the cellular functions of merlin have not been defined [20].

Regulatory relationships of Act42A

• Here, we show that the sole Drosophila ERM protein Moesin functions to promote cortical actin assembly and apical-basal polarity [21].

Other interactions of Act42A

• Two of the genes, act5C and act42A, are expressed in undifferentiated cells and probably encode cytoplasmic actins [22].
• Thus, Moesin functions in maintaining epithelial integrity by regulating cell-signalling events that affect actin organization and polarity [21].
• Cortical binding of oskar mRNA seems to be dependent on the actin cytoskeleton [23].
• We conclude that most of the actin-rich oocyte cortex can support pole plasm assembly, and propose that Kinesin restricts pole plasm formation to the posterior by moving oskar mRNA away from microtubule-rich lateral and anterior cortical regions [23].
• We propose that Crumbs stabilizes the apical SBMS via DMoesin and actin, leading to reinforcement of the ZA and effectively coupling epithelial morphogenesis and cell polarity [24].

Analytical, diagnostic and therapeutic context of Act42A

• The actin loci in the genus Drosophila: establishment of chromosomal homologies among five nearctic species of the Drosophila obscura group by in situ hybridization [25].
• The entire set of six closely related Drosophila actin genes was isolated using recombinant DNA methodology, and the structures of the respective coding regions were characterized by gene mapping techniques and by nucleotide sequencing of selected portions [18].
• Myogenesis in primary cell cultures from Drosophila melanogaster: protein synthesis and actin heterogeneity during development [26].
• By using F-actin affinity chromatography columns to select proteins solely by their ability to bind to actin filaments, we have identified and partially purified greater than 40 proteins from early Drosophila embryos [27].
• First, we use real-time and time-lapsed laser confocal microscopy to follow actin dynamics and document cell shape changes and tissue movements in living, unperturbed embryos [28].

References