Disease relevance of ACTR1A

• ARP-1 is a ubiquitous orphan nuclear receptor that binds to a site (site A) in the apolipoprotein AI (apoAI) liver-specific enhancer and represses its transcriptional activity in hepatoblastoma HepG2 cells [1].
• EXPERIMENTAL DESIGN: PCDGF functions and signaling pathways in dexamethasone-induced apoptosis were studied using a representative dexamethasone-sensitive multiple myeloma cell line ARP-1 [2].
• The same ring-like structure of CTRN expressing neurons was also observed in young polyp buds, predicting the position of the future mouth [3].
• Aberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain [4].

High impact information on ACTR1A

• Morphological and biochemical criteria show that centractin is associated with centrosomes [5].
• Upon nuclear envelope breakdown, large cytoplasmic aggregates of green fluorescent protein (GFP)-tagged NuMA stream poleward along spindle fibers in association with the actin-related protein 1 (Arp1) protein of the dynactin complex and cytoplasmic dynein [6].
• To investigate potential functions of the protein, we used transient transfections to overexpress centractin in mammalian cells [7].
• We examined the transfected cells for evidence of specific associations of the novel centractin filaments with cellular organelles or cytoskeletal proteins [7].
• The primary amino acid sequence of Act3p is most similar to canine and human alpha-centractin (73% similarity/54% identity) [8].

Biological context of ACTR1A

• The amino acid sequence of beta-centractin, deduced from the cDNA, indicates a 91% identity with alpha-centractin, increasing to 96% similarity when conservative amino acid changes are taken into account [9].
• The full-length cDNA clone isolated using the expressed sequence tag encodes a new member of the centractin family, beta-centractin [9].
• Of the ubiquitously expressed members of the Arp superfamily, Arp1 is most similar to conventional actin [4] [5] [6] and, on the basis of conserved sequence features, is predicted to bind ATP and possibly polymerize [10].
• ARP1 in Golgi organisation and attachment of manchette microtubules to the nucleus during mammalian spermatogenesis [11].
• Overexpression of normal and mutant Arp1alpha (centractin) differentially affects microtubule organization during mitosis and interphase [12].

Anatomical context of ACTR1A

• Northern analysis using centractin-specific probes revealed three species of mRNA in HeLa cells that could encode centractin isoforms [9].
• These results demonstrate that p150Glued, a protein implicated in cytoplasmic dynein-based microtubule motility, is capable of direct binding to both microtubules and centractin [13].
• In elongated spermatids, Arp1 was predominantly found along microtubules of the manchette and at their site of attachment to the nuclear envelope [11].
• In maturing spermatids, Arp1 was still present in the pericentriolar material, but in testicular spermatozoa it was not detectable [11].
• This element binds to two members of the steroid hormone receptor superfamily of transcription factors produced in enterocytes and Caco-2 cells: hepatic nuclear factor-4 (HNF-4) and apolipoprotein regulatory protein-1 (ARP-1) [14].

Physical interactions of ACTR1A

• A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1 [15].

Other interactions of ACTR1A

• The TRiC (TCP1 Ring Complex) chaperonin complex participates in the functional folding of actin, centractin, alpha-, beta-, gamma-tubulin, and phytochrome [16].

Analytical, diagnostic and therapeutic context of ACTR1A

• As antibodies previously raised against alpha-centractin reacted only poorly with beta-centractin, new antibodies were produced and combined with two-dimensional gel electrophoresis to discriminate the two isoforms [9].
• Comparisons of Northern blots of human tissues indicated that alpha-centractin and beta-centractin mRNAs are equally distributed in all populations of mRNA examined, whereas the expression of gamma-centractin appears to be tissue specific [9].
• Using immunocytochemistry we observed the colocalization of Golgi marker proteins with the centractin polymers [7].
• Affinity chromatography experiments demonstrate that p62 binds directly to the Arp1 subunit of dynactin [15].
• Anti-Arp1 antibodies were used for western-immunoblotting, indirect immunofluorescence and immunoelectron microscopy [11].

References