Disease relevance of actin

• In a cell culture system, the actin-related protein (Arp) 2/3 complex functions as a nucleation core for actin polymerization when activated by the members of the WASP (Wiskott-Aldrich syndrome protein) family [1].
• In vitro incubation of haemocytes with either Photorhabdus supernatant reduced haemocyte viability, and the W14 supernatant caused distinct changes in the actin cytoskeleton morphology of different haemocyte cell types [2].

High impact information on actin

• All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle [3].
• In hair cells of the inner ear, evidence suggests that an extracellular tip link pulls on a channel, which attached intracellularly to actin via a tension-regulating myosin 1beta [4].
• There is growing evidence that the proteins encoded by these genes interact with key regulators of both the actin and the microtubule cytoskeletons [5].
• Recent insights from this system have determined the involvement in morphogenesis of key proteins, including the actin-regulating WASP and Ena proteins, potential guidance molecules such as the Eph and Robo receptors, and the cell-cell signaling proteins of the Wnt pathway [6].
• Here, we describe a new muscle LIM domain protein, UNC-95, and identify it as a novel target for the RING finger protein RNF-5 in the Caenorhabditis elegans body wall muscle. unc-95(su33) animals have disorganized muscle actin and myosin-containing filaments as a result of a failure to assemble normal muscle adhesion structures [7].

Biological context of actin

• RNA interference of Ce-kettin caused weak disorganization of the actin filaments in body wall muscle [8].
• Although the model refers primarily to the locomotion of nematode sperm, it has important implications for the mechanics of actin-based cell motility [9].
• It is hypothesized that actin plays a role in the shaping of the cell and in the arrangement of its organelles during nematode spermiogenesis, when MSP is present, in an inactive state, in the fibrous bodies [10].
• In Caenorhabditis elegans and Ascaris suum, previous studies have reported that sperm motility does not involve actin, but, instead, requires a specific cytoskeletal protein, namely major-sperm-protein (MSP) [10].
• Analyses of hmp-1, hmp-2, and hmr-1 mutants suggest that products of these genes anchor contractile actin filament bundles at the adherens junctions between hypodermal cells and, thereby, transmit the force of bundle contraction into cell shape change [11].

Anatomical context of actin

• Given these advantages, it has been possible to use C. elegans to investigate the different ways in which the actin cytoskeleton drives the cellular rearrangements underlying morphogenesis, through regulated polymerization or actomyosin contraction [6].
• Tropomyosin shows a distinct pattern in spermatids, but is located in the MSP and actin-containing cap in spermatozoa [10].
• We have studied the localization of actin and MSP in spermatids and spermatozoa of Graphidium strigosum (Dujardin, 1845), a species which has elongate male germ cells in which organelles are easily identified [12].
• Immunocytochemical observations reveal that actin and MSP have an identical localization in precise areas of the male germ cells [12].
• TM4SF10 colocalized with ZO1 and p120ctn in undifferentiated confluent podocytes and also colocalized with the tips of actin filaments at cell contacts [13].

Physical interactions of actin

• UNC-53 is a novel protein conserved in vertebrates that contains putative SH3- and actin-binding sites. unc-53 interacts genetically with sem-5 and we demonstrated a direct interaction in vitro between UNC-53 and the SH2-SH3 adaptor protein SEM-5/GRB2 [14].
• The results indicate that C. elegans actin shares common biochemical properties with rabbit muscle actin, while actin-binding proteins can interact with C. elegans actin in a distinct manner from rabbit muscle actin [15].

Other interactions of actin

• Moreover, nematode sperm lack detectable molecular motors or the battery of actin-binding proteins that characterize actin-based motility [9].
• The increased synthesis of forms of myosin, actin and troponin in the nematode living in the rapid-responder SWR host may relate to the attempted reorganisation or repair of the cytoskeleton and/or muscle layer in the host immune initiated, increased mucus production and smooth muscle activity within intestinal environment [16].
• Sperm of the nematode, Ascaris suum, are amoeboid cells that do not require actin or myosin to crawl over solid substrata [17].
• In the nematode Caenorhabditis elegans, an AIP1 ortholog is encoded by the unc-78 gene that is required for organized assembly of muscle actin filaments [18].
• Here, we performed a detailed characterization of the pha-2 phenotype using cell-type-specific reporters, physical manipulation of the nuclei in pharyngeal muscle cells using "optical tweezers", electron microscopy, staining of the actin cytoskeleton as well as phenotypic rescue and ectopic expression experiments [19].

Analytical, diagnostic and therapeutic context of actin

• The scope of this review is to highlight the numerous roles of the Vav signal transducer proteins in actin organization [20].
• The FBs contain actin as shown by immunofluorescence using a monoclonal anti-actin antibody and by affinity cytochemistry using fluorescent phalloidin [21].

References