Disease relevance of ACT1

• Several recent studies have demonstrated that Wiskott-Aldrich syndrome protein (WASP) family proteins and the actin-related protein (Arp) 2/3 complex are key factors in the nucleation of actin filaments in diverse eukaryotic organisms [1].
• Our findings suggest that changes in the functions or organization of actin filaments might contribute to the establishment of the neoplastic state for these leukemias and lymphomas [2].
• A series of yTm1 N-terminal constructs were made with either an Ala-Ser dipeptide extension previously shown to restore actin binding to skeletal muscle Tm or the natural extension found in fibroblast Tm 5a/b. All constructs bound actin tightly and showed similar CD spectra and thermal stability [3].
• The yeast recombinant Cof produced in Escherichia coli exhibited in vitro activities on actin filaments similar to those of mammalian and avian Cof [4].
• First, it promotes actin assembly on the surface of the motile intracellular pathogen Listeria monocytogenes [5].

Psychiatry related information on ACT1

• This is the first demonstration of an actin-based motor activity in a defined organelle population [6].
• Brownian dynamics simulations of yeast and muscle aldolase and GAPDH with yeast and muscle actin compared the relative association free energy [7].

High impact information on ACT1

• The observation that the BAF chromatin remodeling complex in which actin was originally identified, is also a human tumor suppressor complex necessary for the actions of the retinoblastoma protein indicates that the study of nuclear actin is likely to contribute to understanding cell growth control [8].
• Nuclear actin and actin-related proteins in chromatin remodeling [8].
• In the absence of Cdc42 or Cdc24, the actin cytoskeleton does not become organized and budding does not take place [9].
• Conventional kinesin and class V and VI myosins coordinate the mechanochemical cycles of their motor domains for processive movement of cargo along microtubules or actin filaments [10].
• We show that these diverse formins have the same basic properties: movement is processive in the absence or presence of profilin; profilin accelerates elongation; and actin ATP hydrolysis is not required for processivity [11].

Chemical compound and disease context of ACT1

• Characterization of Slm1 mutants that mimic dephosphorylated and phosphorylated states demonstrated that phosphorylation at serine 659 is vital for survival under heat stress and promotes the proper polarization of the actin cytoskeleton [12].
• Consequently, vaccinia profilin is more likely to influence phosphoinositide metabolism than actin assembly [13].
• The PC/NHERF2/ezrin complex interacts with the actin cytoskeleton, and this interaction is disrupted in GECs from puromycin aminonucleoside-, protamine sulfate-, or sialidase-treated rats, which show a dramatic loss of foot processes, comparable to that seen in the nephrotic syndrome [14].
• A heterologous fusion gene construct was created by attaching the putative promoter sequence and start site from a cryptococcal actin gene to a truncated hygromycin B phosphotransferase gene from E. coli [15].
• Roles for phytosphingosine (PHS) and dihydrosphingosine (DHS) in heat stress continue to be uncovered including regulation of the transient cell cycle arrest, control of putative signaling pathways that govern cell integrity, endocytosis, movement of the cortical actin cytoskeleton and regulation of protein breakdown in the plasma membrane [16].

Biological context of ACT1

• Diploid cells containing a single copy of ACT1 are osmosensitive (Osms), i.e., they fail to grow in high osmolarity media (D. Shortle, unpublished observations cited by Novick, P., and D. Botstein. 1985. Cell. 40:415-426) [17].
• Molecular genetic analysis indicates ACT3 is represented by a single gene from which the corresponding mRNA is expressed at a low level compared to ACT1 [18].
• To understand the RNA structural features that dictate mRNA decay rates in yeast, we have constructed PGK1/MAT alpha 1 and ACT1/MAT alpha 1 gene fusions and analyzed the decay rates of the resultant chimeric transcripts [19].
• Primer extension analysis showed that the aar2 mutant and disruptant have a defect in splicing two short introns of the a1 pre-mRNA but not in splicing pre-mRNA of ACT1 [20].
• Interestingly, we also observed that mutation of the poly(A) polymerase gene altered the site of ACT1 polyadenylation [21].

Anatomical context of ACT1

• Finally, a yeast mutant bearing a temperature-sensitive mutation in the actin-encoding ACT1 gene (act1-3) displays temperature-dependent defects in transfer of mitochondria from mother cells to newly developed buds during yeast cell mitosis [22].
• In both animal and yeast cells, this process is dependent on cytoplasmic microtubules interacting with the cortical actin-based cytoskeleton, although the motive force was unknown [23].
• Actin, a major cytoskeletal component of all eukaryotic cells, is one of the most highly conserved proteins [24].
• Vac8p is related to beta-catenin and plakoglobin, which connect a specific region of the plasma membrane to the actin cytoskeleton [25].
• Double deletion mutants also display phenotypes associated with actin disorganization including accumulation of intracellular membranes and vesicles, cell rounding, random bud site selection, sensitivity to high osmotic strength, and low pH as well as defects in chitin and cell wall deposition, invertase secretion, and fluid phase endocytosis [26].

Associations of ACT1 with chemical compounds

• Twelve "alanine scan" alleles of the single yeast actin gene (ACT1) were tested for effects on filamentation, unipolar budding, agar invasion, and cell elongation [27].
• In comparison to CLN2, expression from the ACT1 promoter was stable after release from nocodazole [28].
• Irrespective of whether induction was achieved with methanol or formate, the UAS-FM element enhanced the level of induction of the FDH1 promoter in a manner dependent on the number of copies, but independent of their orientation, and also converted the ACT1 promoter from a constitutive into an inducible element [29].
• We report that the actin assembly inhibitor latrunculin-A (LAT-A) causes complete disruption of the yeast actin cytoskeleton within 2-5 min, suggesting that although yeast are nonmotile, their actin filaments undergo rapid cycles of assembly and disassembly in vivo [30].
• Regulation of the actin cytoskeleton organization in yeast by a novel serine/threonine kinase Prk1p [31].

Physical interactions of ACT1

• Thus Sac6p binds to actin in vitro, and functionally associates with actin structures involved in the development and maintenance of cell polarity in vivo [32].
• The yeast IQGAP homologue, designated Iqg1p, displays a two-hybrid interaction with activated Cdc42p and coimmunoprecipitates with actin filaments [33].
• Using the two-hybrid system, we show that verprolin binds actin [34].
• The F-actin-binding activity of unacetylated Tpm1p is reduced severely relative to the acetylated form [35].
• Through systematic mutagenesis of Aip1 surfaces, we identify two well-separated F-actin-binding sites, one of which contributes to actin filament binding and disassembly specifically in the presence of cofilin [36].

Enzymatic interactions of ACT1

• In vivo importance of actin nucleotide exchange catalyzed by profilin [37].
• Yeast actin mutants with acidic residues at the N terminus either neutralized (DNEQ) or deleted (delta-DSE) were used to assess the role of N-terminal acidic residues in the interactions of actin with myosin in the contractile cycle [38].

Co-localisations of ACT1

• In fixed cells hemagglutinin-tagged Vrp1p often co-localizes with actin in cortical patches [34].
• Immunofluorescence staining revealed that the Pan1 protein colocalized with the cortical actin patches, suggesting that it may be a filamentous actin-binding protein [39].
• Furthermore, Scp1p co-localizes with actin in cortical patches and its localization is lost in the presence of latrunculin-A [40].
• Consistent with a role in cytokinesis, Iqg1 co-localizes with an actin ring encircling the mother-bud neck late in the cell cycle -a putative cytokinetic ring [41].
• Rvs167p colocalized with actin patches during yeast vegetative growth and mating [42].

Regulatory relationships of ACT1

• Bni1p and Bnr1p: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae [43].
• These results suggest that Cdc42 is closely involved in regulating actin assembly during polarized cell growth [44].
• Previously we reported that additional actin suppresses the temperature-dependent growth defect caused by a mutation in VRP1 [34].
• Cdc28p activated by G1-cyclins triggers polarization of actin to the site of bud emergence and favors apical bud growth (Lew, D. J., and S. I. Reed. 1993. J. Cell Biol. 120:1305-1320) [45].
• These results indicate that Bni1p regulates microtubule-dependent nuclear migration through the actin cytoskeleton [46].

Other interactions of ACT1

• To our knowledge, the Act2 protein from S. cerevisiae is the first highly divergent actin molecule described [24].
• Requirement of yeast fimbrin for actin organization and morphogenesis in vivo [32].
• Bni1p may function as a Cdc42p target that links the pheromone response pathway to the actin cytoskeleton [47].
• During mating pheromone response, bni1 mutants showed defects both in polarized morphogenesis and in reorganization of the underlying actin cytoskeleton [47].
• This defect is seen not only in 3' splice site cis-competitions but also in the splicing of an unusual intron in the TUB3 gene and in the ACT1 intron when utilization of its 3' splice site is rate limiting for splicing [48].

Analytical, diagnostic and therapeutic context of ACT1

• According to the partial sequence of ACT1 gene and flow cytometry analysis, strain CID1 is a triple hybrid between S. cerevisiae, S. kudriavzevii and S. bayanus var. uvarum [49].
• Using Northern blot analysis we have detected an approximately 840 nucleotide-long RNA which is complementary to the 5' leader sequence and the first ten nucleotides of the coding sequence of the yeast actin (ACT1) messenger RNA [50].
• Actin patches were partially purified from Saccharomyces cerevisiae and examined by negative-stain electron microscopy (EM) [51].
• Immunofluorescence experiments showed that, like Abp1p, cofilin is associated with the membrane actin cytoskeleton [52].
• Although defective in nuclear import, act2-1 cells still selectively retain reporter proteins in the nucleus, and by indirect immunofluorescence the actin cytoskeleton appears normal [53].

References