save as scar_wave

 The conserved Scar/Wave and Vrp1/WASp pathways for Arp2/3 activation
http://dev.biologists.org/content/139/4/641

The Actin-related protein 2/3 (Arp2/3) complex is a conserved mediator of actin polymerization. It controls the formation of branched actin networks by binding to pre-existing filaments and promoting formation of new filaments by branching. This complex is activated by actin nucleation-promoting factors (NPFs) that include Suppressor of cAMP Receptor/WASp family Verprolin-homologous (Scar/Wave) (Scar in Drosophila; Wave in vertebrates) and Wiskott-Aldrich syndrome protein (WASp) (Machesky and Insall, 1998; Padrick et al., 2011). Scar/Wave exists in an inactive complex with Abi (Abl interactor protein), Kette/Nck-associated protein 1 (Nap1), Sra1 (Specifically Rac1-associated protein) and Brk1/Hspc300 (Breast tumor kinase/hematopoietic stem/progenitor cell protein 300) (Eden et al., 2002; Derivery and Gautreau, 2010; Kurisu and Takenawa, 2010) (see A). In this complex, the C-terminal verprolin central acidic (VCA) domain is blocked by interaction with Abi and Kette/Nap1 (Kim et al., 2000). Activation occurs upon binding of the complex to the small GTPase Rac1, releasing the VCA domain to bind to, and activate, the Arp2/3 complex (Kobayashi et al., 1998; Lebensohn and Kirschner, 2009). Some studies have suggested that Rac1 disrupts binding of the inhibitory Abi and Kette/Nap1 proteins (Ismail et al., 2009). However, more recent studies indicate that activated Rac1 alters the conformation of the Scar/Wave complex but does not physically disrupt it (Chen et al., 2010; Derivery and Gautreau, 2010). Arf GTPases may also activate Scar/Wave (Koronakis et al., 2011). The WASp NPF (see B) also activates the Arp2/3 complex and is present in the cell in an inactive state. Vrp1/Wip functions to stabilize WASp, protect it from degradation and contribute to its activation (Martinez-Quiles et al., 2001; Chou et al., 2006; Anton et al., 2007; de la Fuente et al., 2007). Similar to Scar/Wave, WASp is activated by protein binding to the autoinhibitory GTPase-binding domain (GBD), thereby releasing the VCA domain. Vrp1/Wip is also important for translocation of WASp to sites of actin polymerization.


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Genes and pathways associated with myoblast fusion in Drosophila

http://dev.biologists.org/content/139/4/641

saved as myoblastfusion.jpg

Genes and pathways associated with myoblast fusion in Drosophila. The indicated genes and pathways correspond to those, as discussed in the text, that appear to function in founder cells/myotubes and fusion-competent myoblasts of Drosophila embryos. The represented proteins include those for which a role in fusion has been shown experimentally. Generally, these comprise components of the Rac1, Scar and WASp pathways and their regulators, cell-adhesion molecules, and essential proteins such as Sing, for which a mechanistic role remains to be elucidated. In most instances, demonstration of an involvement in myoblast fusion has been established by direct loss-of-function studies experimentally. For some proteins, a role is inferred by biochemical interaction with known fusion proteins. Relationships indicated by broken lines are based on protein functions in other tissues, but have not yet been established in this system. Arp2/3, Actin-related protein 2/3; Ants, Antisocial; Arf6, ADP ribosylation factor 6; Blow, Blown Fuse; Crk, CT10 regulator of Kinase; Elmo, Engulfment and cell motility protein; GEF, Guanine nucleotide exchange factor; Hbs, Hibris; Kirre, Kin-of IrreC; Mbc, Myoblast city; PIP3, Phosphatidylinositol (3,4,5) triphosphate; Rac1, Ras-related C3 botulinum toxin substrate 1; Rst, Roughest; Sltr, Solitary; Rols7, Rolling pebbles isoform 7; Scar, Suppressor of cAMP receptor; Sing, Singles-bar; Sns, Sticks and stones; Vrp1, Verprolin 1; WASp, Wiscott-Aldrich syndrome protein; Wip, Drosophila WASp-interacting protein.

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<P>Ren, F., Wang, B., Yue, T., Yun, E. Y., Ip, Y. T. and Jiang, J. (2010). Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci U S A 107: 21064-21069. PubMed ID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21078993">21078993</a>


Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways 

http://www.pnas.org/content/107/49/21064/F6.expansion.html

Fig. 6.

Hpo signaling regulates ISC proliferation through both cell-autonomous and non–cell-autonomous mechanisms. Hpo/Wts restricts the activity of Yki in the precursor cells to inhibit ISC proliferation. This cell-autonomous mechanism could be regulated by contact between ISC and basement membrane (BM), which is disrupted by DSS. Hpo signaling also acts in the ECs to restrict the production of ligands for the JAK-STAT and EGFR pathways, thereby inhibiting ISC proliferation by limiting the activities of these two pathways. Bleomycin and possibly PE cause damage of ECs and induce ISC proliferation through Yki-dependent and Yki-independent mechanisms. Of note, each arrow does not necessarily mean direct regulation. 

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<P>Buchon, N., Broderick, N. A. and Lemaitre, B. (2013). Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat Rev Microbiol 11: 615-626. PubMed ID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/23893105">23893105</a>
	Intestinal homeostasis is achieved, in part, by the integration of a complex set of mechanisms that eliminate pathogens and tolerate the indigenous microbiota. Drosophila melanogaster feeds on microorganism-enriched matter and therefore has developed efficient mechanisms to control ingested microorganisms. Regulatory mechanisms ensure an appropriate level of immune reactivity in the gut to accommodate the presence of beneficial and dietary microorganisms, while allowing effective immune responses to clear pathogens. Maintenance of D. melanogaster gut homeostasis also involves regeneration of the intestine to repair damage associated with infection. Entomopathogenic bacteria have developed common strategies to subvert these defence mechanisms and kill their host.

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http://www.nature.com/nrmicro/journal/v11/n9/images/nrmicro3074-f3.jpg

Regulation of reactive oxygen species production in the Drosophila melanogaster midgut.

http://www.nature.com/nrmicro/journal/v11/n9/fig_tab/nrmicro3074_F3.html
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<P>Buchon, N., Broderick, N. A. and Lemaitre, B. (2013). Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat Rev Microbiol 11: 615-626. PubMed ID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/23893105">23893105</a>

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