Suppressor of profilin 2 : Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References
Gene name - Actin-related protein 2/3 complex, subunit 1

Synonyms - Sop2, Suppressor of profilin 2,

Cytological map position - 34D6

Function - signaling

Keywords - cytoskeleton, actin polymerization, Arp2/3 complex, oogenesis, cellularization, PNS

Symbol - Arpc1

FlyBase ID: FBgn0001961

Genetic map position -

Classification - WD repeat protein

Cellular location - cytoplasm

NCBI links: Precomputed BLAST | Entrez Gene | UniGene

Recent literature

Hsiao, J. Y., Goins, L. M., Petek, N. A. and Mullins, R. D. (2015). Arp2/3 complex and cofilin modulate binding of tropomyosin to branched actin networks. Curr Biol 25: 1573-1582. PubMed ID: 26028436.
Tropomyosins are coiled-coil proteins that bind actin filaments and regulate multiple cytoskeletal functions, including actin network dynamics near the leading edge of motile cells. Tropomyosins inhibit actin nucleation by the Arp2/3 complex and prevent filament disassembly by cofilin. This study finds that the Arp2/3 complex and cofilin, in turn, regulate the binding of tropomyosin to actin filaments. Using fluorescence microscopy, this study showed that tropomyosin (non-muscle Drosophila Tm1A) polymerizes along actin filaments, starting from "nuclei" that appear preferentially on ADP-bound regions of the filament, near the pointed end. Tropomyosin fails to bind dendritic actin networks created in vitro by the Arp2/3 complex, in part because the Arp2/3 complex blocks pointed ends. Cofilin promotes phosphate dissociation and severs filaments, generating new pointed ends and rendering Arp2/3-generated networks competent to bind tropomyosin. Tropomyosin's attraction to pointed ends reveals a basic molecular mechanism by which lamellipodial actin networks are insulated from the effects of tropomyosin.

Tran, D. T., Masedunskas, A., Weigert, R. and Ten Hagen, K. G. (2015). Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo. Nat Commun 6: 10098. PubMed ID: 26639106
The actin cytoskeleton plays crucial roles in many cellular processes, including regulated secretion. However, the mechanisms controlling F-actin dynamics in this process are largely unknown. Through 3D time-lapse imaging in a secreting organ, this study shows that F-actin is actively disassembled along the apical plasma membrane at the site of secretory vesicle fusion and re-assembled directionally on vesicle membranes. Moreover, fusion pore formation and PIP2 redistribution was shown to precedes actin and myosin recruitment to secretory vesicle membranes. Finally, essential roles were shown for the branched actin nucleators Arp2/3- and WASp in the process of secretory cargo expulsion and integration of vesicular membranes with the apical plasma membrane. These results highlight previously unknown roles for branched actin in exocytosis and provide a genetically tractable system to image the temporal and spatial dynamics of polarized secretion in vivo.


The Arp2/3 complex dramatically increases the slow spontaneous rate of actin filament nucleation in vitro, and it is known to be important for remodeling the actin cytoskeleton in vivo. Suppressor of Profilin 2 or Sop 2 (alternative name: Arpc1), is one of the components of this complex. Loss of function mutations in genes encoding two subunits, Arpc1 (which encodes the homolog of the p40 subunit), and Arp3 (encoding one of the two actin-related proteins), have been isolated and characterized. These mutations were used to study how the Arp2/3 complex contributes to well-characterized actin structures in the ovary and the pupal epithelium. The Arp2/3 complex has been found to be required for ring canal expansion during oogenesis but not for the formation of parallel actin bundles in nurse cell cytoplasm and bristle shaft cells. The requirement for Arp2/3 in ring canals indicates that the polymerization of actin filaments at the ring canal plasma membrane is important for driving ring canal growth (Hudson, 2002).

It is well established that the Arp2/3 complex requires activation by proteins of the Wasp/Scar family. Requirements for the Arp2/3 complex have been characterized in maintaining ring canal integrity and also in the production of the ridging pattern in mechanosensory bristles. Strong alleles of SCAR, which encodes the single Drosophila Scar/Wave protein, display an oogenesis phenotype similar to Arp2/3 complex mutations (Zahlen, 2002). In contrast, germline clones of strong Wasp alleles proceed through oogenesis with no apparent defects. Thus, Drosophila SCAR may be an important activator of the Arp2/3 complex during oogenesis (Hudson, 2002).

The Arp2/3 complex is also required for psuedocleavage furrow assembly in syncytial Drosophila embryos. In syncytial blastoderm Drosophila embryos, actin caps assemble during telophase. These caps consist of accumulated actin within plasma membrane bulges that lie above each newly formed daughter nucleus. As the cell cycle progresses through interphase, these small caps expand and fuse to form pseudocleavage furrows that are structurally related to the cleavage furrows that assemble during somatic cell division. The molecular mechanism driving cell cycle coordinated actin reorganization from the caps to the furrows is not understood. Drosophila embryos are shown to contain a typical Arp2/3 complex and components of this complex localize to the margins of the expanding caps, to mature pseudocleavage furrows, and to somatic cell cleavage furrows during the postcellularization embryonic divisions. A mutation that disrupts the arpc1 subunit of Arp2/3 leads to spindle fusions that are characteristic of pseudocleavage furrow disruption. By contrast, this mutation does not significantly affect nuclear positioning during interphase, which is dependent on actin cap function. In vivo analysis of actin reorganization demonstrates that the arpc1 mutation does not prevent assembly of small actin caps but blocks cap expansion and furrow assembly as the cell cycle progresses through interphase. The scrambled gene is also required for cap expansion and furrow assembly, and Scrambled is required for Arp2/3 localization to the cap margins. Therefore, the Drosophila Arp2/3 complex and Scrambled protein are required for actin cap expansion and pseudocleavage furrow formation during the syncytial blastoderm divisions. It is proposed that Scrambled-dependent localization of Arp2/3 to the margins of the expanding caps triggers local actin polymerization that drives cap expansion and pseudocleavage furrow assembly (Stevenson, 2002).

Cell division and accurate chromosome segregation depend on spatially and temporally coordinated changes in nuclear and cytoskeletal organization. In somatic cells, entry into mitosis triggers disassembly of interphase microtubule and actin arrays, spindle formation, nuclear envelope breakdown, and chromosome condensation. On exit from mitosis, spindle disassembly and formation of the actin-based contractile ring are coordinated with chromosome segregation, chromosome decondensation, and nuclear envelope formation. In S. pombe and S. cerevisiae, genetic studies have defined pathways controlling actin reorganization on exit from mitosis. In higher eukaryotes, however, the molecular mechanisms controlling cytoskeletal reorganization during mitotic progression are less well understood. The cleavage plane appears to be specified by the position of the spindle during metaphase or anaphase, when a number of proteins localize to the site where the furrow will form. Actin filaments subsequently accumulate at this site and organize into the contractile ring, which constricts to cleave the cell. It is unclear if spindle asters or the central spindle provide the positional information that defines the cleavage plane, and there is evidence that both structures have a role in this process. In addition, the molecular pathways linking the spindle poles and/or central spindle to actin reorganization and the source of filamentous actin in the contractile ring remain to be defined (Stevenson, 2002).

In syncytial blastoderm stage Drosophila embryos, dramatic changes in actin organization accompany rapid divisions that occur in a cortical nuclear monolayer. During each nuclear division cycle, mitotic exit leads to actin accumulation within plasma membrane bulges that lie above each newly formed daughter nucleus. These actin and membrane based bulges, referred to as actin caps, expand though interphase and fuse to form pseudocleavage furrows that surround the cortical spindles at the next mitosis. The pseudocleavage furrows share a number of components with the cleavage furrows that form during somatic cell division, suggesting that these are related actin structures. While actin is essential to assembly of both pseudocleavage and true cleavage furrows, the mechanism of actin filament polymerization in these structures has not been determined (Stevenson, 2002).

The Arp2/3 complex is the best-characterized actin-nucleating factor in somatic cells. This conserved complex has been implicated in membrane extension during cell migration and in motility of intracellular pathogens but has not been previously shown to have a cell cycle-specific function. Early Drosophila embryos are shown to contain a typical Arp2/3 complex and two components of this complex localize to the leading edge of expanding actin caps and to mature pseudocleavage furrows. Furthermore, a mutation in the Arpc1 subunit of the Arp2/3 complex disrupts actin cap expansion, leading to a failure in pseudocleavage assembly and function. Interestingly, the arpc1 mutation does not prevent cap assembly. The actin-based caps and furrows thus have differential requirements for Arp2/3, with this conserved complex playing a particularly critical role during cap expansion and furrow assembly. Based on these observations, a model is proposed in which actin cap expansion and pseudocleavage furrow assembly are driven by Arp2/3-mediated actin polymerization (Stevenson, 2002).

To examine Arp2/3 function during the syncytial blastoderm stage, attempts were made to identify and analyze mutations that disrupt components of this complex. The syncytial blastoderm divisions do not require zygotic gene expression and are driven by material deposited in the oocyte during oogenesis. Therefore, mutations that allow adult female development and egg production but disrupt Arp2/3 function in the oocyte were required for these studies. The Arpc1 gene encodes the p41 subunit of Arp2/3, and several alleles of Arpc1 have been generated by EMS mutagenesis (Hudson, 2002). These mutations are lethal and thus block development of homozygous adult females. However, germline clones of these mutations can be generated within heterozygous adult females. Clones of stronger alleles disrupt oogenesis and block egg production, but germline clones of the Arpc1r337st allele, which has a nonsense mutation at residue 337 yielding a truncated protein, produce embryos (referred to as Arpc1r337st embryos) (Stevenson, 2002).

To characterize the effects of Arp2/3 disruption on the syncytial mitotic divisions, embryos were injected with fluorescent conjugates of tubulin, and centrosome and microtubule behavior were analyzed. In wild-type embryos, interphase nuclei and mitotic spindles remain uniformly spaced within the cortical monolayer during the syncytial blastoderm divisions. The arpc1r337st mutant embryos appear relatively normal through division 10 to 11 but show spindle interactions and chromosome segregation errors that increase in frequency during divisions 12 and 13. In contrast to these severe mitotic defects, the arpc1r337st mutation does not produce dramatic defects in the spacing of interphase nuclei. Occasionally, free centrosomes are observed in these embryos. However, the vast majority of interphase nuclei have a normal complement of centrosomes, and the mutation does not appear to have a significant effect on centrosome association with the nuclear envelope. Interactions between neighboring spindles are characteristic of defects in pseudocleavage furrow formation, while defects in actin cap function lead to dramatic clustering of interphase nuclei. The uniform spacing of interphase nuclei combined with frequent spindle fusions thus strongly suggests that the arpc1 mutant disrupts pseudocleavage furrows function without seriously compromising the function of interphase caps (Stevenson, 2002).

To directly examine the effect of the arpc1r337st mutation on cell cycle-regulated actin reorganization, arpc1r337st embryos were injected with fluorescent actin conjugates and imaged by time-lapse confocal microscopy. In wild-type embryos, small interphase actin caps form on mitotic exit, and these caps expand continuously through interphase. Actin redistributes to the margins of the caps as they expand and merge to form pseudocleavage furrows. In arpc1r337st embryos, pronounced actin caps assemble on mitotic exit. However, these caps are smaller than normal, actin never redistributes to the cap margins, and the caps fail to expand. Late in the cell cycle, actin disperses, and pseudocleavage furrow assembly fails. Interphase actin caps reform during the next telophase, and the cycle of defective cap expansion is repeated (Stevenson, 2002).

To gain further insight into actin defects in arpc1 mutants, embryos were fixed and labeled for f-actin with rhodamine-phalloidin. In wild-type embryos, robust actin-based pseudocleavage furrows extend into the embryo during late interphase and mitosis. In arpc1r337st embryos, by contrast, only superficial actin rings are present during mitosis. These shallow actin rings do not completely surround spindles and do not extend significantly into the interior of the embryo. These observations, with the analysis of nuclear spacing and spindle assembly, indicate that wild-type Arp1c function is essential to cap expansion and pseudocleavage furrow formation (Stevenson, 2002).

The role of Arp2/3 in cap assembly is less clear. The arpc1r337st mutation used in these studies is a partial loss of function allele, and the actin caps that form in arpc1r337st embryos are smaller than normal. It is therefore possible that Arp2/3 function is needed for cap morphogenesis, and the low levels of Arp2/3 function in the arpc1r337stmutants are sufficient to support assembly of small caps. It is also possible that actin assembly in the caps is completely independent of Arp2/3. The available data are not sufficient to distinguish between these alternatives (Stevenson, 2002).

The arpc1r337st mutation does not block blastoderm cellularization, consistent with the absence of Arp3 at the cellularization furrow canal. However, gene transcription increases dramatically during division cycle 14, and zygotic expression of functional Arpc1 from the paternal allele could support this process (Stevenson, 2002).

The accumulation of Arp2/3 complex at the margins of the expanding caps and the specific defects in actin cap expansion and furrow assembly in arpc1r337st mutants suggest a filament polymerization-based model for cell cycle-regulated actin reorganization in the early embryo. In this model, Arp2/3 localization to the edges of the early interphase caps leads to localized actin polymerization that powers the outward membrane movements of cap expansion. The pseudocleavage furrows are then formed as the neighboring caps meet. In this model, pseudocleavage furrow maturation is mechanistically related to membrane protrusion in migrating cells or to intracellular pathogen motility but is distinct from the actomyosin-based process that appears to drive cytokinesis in somatic cells. Consistent with this hypothesis, mutations in the myosin light chain gene and injection of antibodies to myosin heavy chain do not produce severe defects in pseudocleavage furrow assembly. However, other myosins could mediate pseudocleavage furrow assembly, and the possibility that Arp2/3 nucleates actin filaments that subsequently serve as substrates for myosin-based contraction cannot be ruled out (Stevenson, 2002 and references therein).

The mechanism of Arp2/3 localization during furrow assembly is not known. However, the defects in actin reorganization produced by the arpc1 mutation are strikingly similar to the defects produced by mutations in the scrambled gene, and the Scrambled protein also localizes to the margins of the caps and to furrows (Stevenson, 2001). Arp3 fails to localize to the margins of the caps that form in scrambled mutant embryos, suggesting that Scrambled may recruit Arp2/3 to the cap margins. The Scrambled protein shows no significant homology to other proteins and lacks clear functional domains, and Arp2/3 components do not coimmunoprecipitate or copurify with Scrambled. The mechanism of Scrambled-dependent Arp2/3 localization is therefore unclear. Drosophila SCAR is also required for furrow assembly, and Scar/WAVE proteins are know to activate the Arp2/3 complex. These observations raise the possibility that Scrambled may interact with Scar to localize and activate Arp2/3 at the furrow margins (Stevenson, 2002).

The mechanism of actin filament polymerization during cytokinesis has not been determined, but localization of Arp3 to contractile rings during the postcellularization divisions raises the possibility that Arp2/3 mediates actin assembly during conventional cleavage. Arp2/3 is maternally deposited, and maternal protein pools remain active through the postcellularization somatic cell divisions. As a result, the available lethal arp1c alleles do not allow an analysis of Arp2/3 function during these divisions. However, it may be possible to disrupt Arp2/3 function during the postcellularization divisions by RNAi. Analysis of the larval mitoses in animals mutant for lethal arpc1 alleles may also provide insight into the function of this complex during conventional cytokinesis (Stevenson, 2002).


cDNA clone length - 1706 bp

Bases in 5' UTR - 288

Exons - 2

Bases in 3' UTR - 384


Amino Acids - 377

Structural Domains

Structural information related to Sop2 can be found at NiceProt View of TrEMBL: O97182

Suppressor of profilin 2 : Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

date revised: 15 December 2003

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