Genomes and Genes
Gene Symbol: Hrs
Description: Hepatocyte growth factor regulated tyrosine kinase substrate
Alias: CG2903, DmHRS, Dmel\CG2903, HRS, HRS-2, Vps27, dHrs, hrs, l(2)23AB5, l(2)23Ad, l(2)23Ad(Hrs), vps27, hepatocyte growth factor regulated tyrosine kinase substrate, CG2903-PA, CG2903-PB, CG2903-PC, F[]F[] ATPase, HGF-regulated tyrosine kinase substrate, Hrs-PA, Hrs-PB, Hrs-PC, hepatocyte growth factor regulated tyrosine kinase, hepatocyte growth factor-regulated tyrosine kinase substrate, hepatocyte growth factor-regulated tyrosine substrate, hepatocyte growth-factor-regulated substrate
Species: fruit fly
- Wilkin M, Carbery A, Fostier M, Aslam H, Mazaleyrat S, Higgs J, et al. Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr Biol. 2004;14:2237-44 pubmed..Instead, we show that Su(dx) regulates the postendocytic sorting of Notch within the early endosome to an Hrs- and ubiquitin-enriched subdomain en route to the late endosome...
- Wang W, Struhl G. Drosophila Epsin mediates a select endocytic pathway that DSL ligands must enter to activate Notch. Development. 2004;131:5367-80 pubmed..Alternatively Epsin may be required to target mono-ubiquitinated DSL proteins to a particular subclass of coated pits that have special properties essential for Notch activation. ..
- Schneider M, Troost T, Grawe F, Martinez Arias A, Klein T. Activation of Notch in lgd mutant cells requires the fusion of late endosomes with the lysosome. J Cell Sci. 2013;126:645-56 pubmed publisher..In addition, electron microscopy of lgd cells revealed that they contain enlarged multi-vesicular bodies. The presented results further elucidate the mechanism of uncontrolled Notch activation upon derailed endocytosis...
- Juhasz G, Hill J, Yan Y, Sass M, Baehrecke E, Backer J, et al. The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol. 2008;181:655-66 pubmed publisher..Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation. ..
- Haberman A, Williamson W, Epstein D, Wang D, Rina S, Meinertzhagen I, et al. The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration. J Cell Biol. 2012;196:261-76 pubmed publisher..Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity. ..
- Michelet X, Djeddi A, Legouis R. Developmental and cellular functions of the ESCRT machinery in pluricellular organisms. Biol Cell. 2010;102:191-202 pubmed publisher..The present review summarizes recent research on the developmental and cellular functions of the ESCRT in Caenorhabditis elegans, Drosophila melanogaster, Mus musculus or Arabidopsis thaliana. ..
- Devergne O, Ghiglione C, Noselli S. The endocytic control of JAK/STAT signalling in Drosophila. J Cell Sci. 2007;120:3457-64 pubmed..blocking trafficking in distinct endosomal compartments using mutants affecting either Clathrin heavy chain, rab5, Hrs or deep orange led to an inhibition of the JAK/STAT pathway, whereas this pathway was unchanged when rab11 was ..
- Childress J, Acar M, Tao C, Halder G. Lethal giant discs, a novel C2-domain protein, restricts notch activation during endocytosis. Curr Biol. 2006;16:2228-33 pubmed..Interestingly, Notch activation in lgd mutant cells requires the early endosomal component Hrs, indicating that Hrs is epistatic to Lgd...
- DiAntonio A, Parfitt K, Schwarz T. Synaptic transmission persists in synaptotagmin mutants of Drosophila. Cell. 1993;73:1281-90 pubmed..The lethality of synaptotagmin in late first instar larvae is probably due to a perturbation of transmission that leaves the main apparatus for vesicle docking and fusion intact. ..
- Sweeney S, Davis G. Unrestricted synaptic growth in spinster-a late endosomal protein implicated in TGF-beta-mediated synaptic growth regulation. Neuron. 2002;36:403-16 pubmed..Furthermore, mutations in Dad, an inhibitory Smad, cause synapse overgrowth. We present a model for synaptic growth control with implications for the etiology of lysosomal storage and neurodegenerative disease. ..
- Lu H, Bilder D. Endocytic control of epithelial polarity and proliferation in Drosophila. Nat Cell Biol. 2005;7:1232-9 pubmed..Our findings reveal a critical and specific role for endocytic traffic in the control of both apico-basal polarity and cell proliferation. ..
- Jekely G, Rørth P. Hrs mediates downregulation of multiple signalling receptors in Drosophila. EMBO Rep. 2003;4:1163-8 pubmed..A key step regulating the degradation of receptors is their ubiquitination. Hrs/Vps27p, an endosome-associated, ubiquitin-binding protein, affects sorting and degradation of receptors...
- Issman Zecharya N, Schuldiner O. The PI3K class III complex promotes axon pruning by downregulating a Ptc-derived signal via endosome-lysosomal degradation. Dev Cell. 2014;31:461-73 pubmed publisher..By studying several PI(3)P binding proteins, we found that Hrs, a subunit of the ESCRT-0 complex, required for multivesicular body (MVB) maturation, is essential for normal ..
- Lloyd T, Atkinson R, Wu M, Zhou Y, Pennetta G, Bellen H. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell. 2002;108:261-9 pubmed..However, factors that regulate endosomal sorting of TKRs are largely unknown. Here, we demonstrate that Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) is one such factor...
- Rives A, Rochlin K, Wehrli M, Schwartz S, Dinardo S. Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. Dev Biol. 2006;293:268-83 pubmed..pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner...
- Lee O, Frese K, James J, Chadda D, Chen Z, Javier R, et al. Discs-Large and Strabismus are functionally linked to plasma membrane formation. Nat Cell Biol. 2003;5:987-93 pubmed..This effect was dependent on the interaction between Stbm and SAP97. These findings suggest that the Dlg-Stbm complex recruits membrane-associated proteins and lipids from internal membranes to sites of new plasma membrane formation. ..
- Yousefian J, Troost T, Grawe F, Sasamura T, FORTINI M, Klein T. Dmon1 controls recruitment of Rab7 to maturing endosomes in Drosophila. J Cell Sci. 2013;126:1583-94 pubmed publisher..This was the case even when receptor uptake into intraluminal vesicles was suppressed...
- Rusten T, Vaccari T, Lindmo K, Rodahl L, Nezis I, Sem Jacobsen C, et al. ESCRTs and Fab1 regulate distinct steps of autophagy. Curr Biol. 2007;17:1817-25 pubmed..Thus, this study links ESCRT function with autophagy and aggregate-induced neurodegeneration, thereby providing a plausible explanation for the fact that ESCRT mutations are involved in inherited neurodegenerative disease in humans . ..
- Blankenship J, Fuller M, Zallen J. The Drosophila homolog of the Exo84 exocyst subunit promotes apical epithelial identity. J Cell Sci. 2007;120:3099-110 pubmed..These results suggest that epithelial polarity in the Drosophila embryo is actively maintained by exocyst-dependent apical localization of the Crumbs transmembrane protein. ..
- Irion U, St Johnston D. bicoid RNA localization requires specific binding of an endosomal sorting complex. Nature. 2007;445:554-8 pubmed..This function of ESCRT-II as an RNA-binding complex is conserved in vertebrates and may clarify some of its roles that are independent of endosomal sorting. ..
- Emery G, Hutterer A, Berdnik D, Mayer B, Wirtz Peitz F, Gaitan M, et al. Asymmetric Rab 11 endosomes regulate delta recycling and specify cell fate in the Drosophila nervous system. Cell. 2005;122:763-73 pubmed..Our results suggest that cells can regulate signaling pathways and influence their developmental fate by inhibiting the formation of individual endocytic compartments...
- Langevin J, Morgan M, Sibarita J, Aresta S, Murthy M, Schwarz T, et al. Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. Dev Cell. 2005;9:365-76 pubmed..Our results support a model whereby the exocyst regulates DE-Cadherin trafficking, from recycling endosomes to sites on the epithelial cell membrane where Armadillo is located. ..
- Tjota M, Lee S, Wu J, Williams J, Khanna M, Thomas G. Annexin B9 binds to ?(H)-spectrin and is required for multivesicular body function in Drosophila. J Cell Sci. 2011;124:2914-26 pubmed publisher..in an increase in basolateral ?(H) and its appearance on cytoplasmic vesicles that overlap with the MVB markers Hrs, Vps16 and EPS15...
- Chanut Delalande H, Jung A, Baer M, Lin L, Payre F, Affolter M. The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development. PLoS ONE. 2010;5:e10245 pubmed publisher..b>Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will ..
- Beckett K, Monier S, Palmer L, Alexandre C, Green H, Bonneil E, et al. Drosophila S2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes. Traffic. 2013;14:82-96 pubmed publisher..Consistent with this conclusion, extracellularly tagged Evi expressed from a Bacterial Artificial Chromosome is not released from imaginal disc Wingless-expressing cells. ..
- Akbar M, Ray S, KRAMER H. The SM protein Car/Vps33A regulates SNARE-mediated trafficking to lysosomes and lysosome-related organelles. Mol Biol Cell. 2009;20:1705-14 pubmed publisher..Consistent with a role in Car-mediated fusion, dSyntaxin16 is not restricted to Golgi membranes but also present on lysosomes. ..
- Le Borgne R, Schweisguth F. Unequal segregation of Neuralized biases Notch activation during asymmetric cell division. Dev Cell. 2003;5:139-48 pubmed..We propose that coordinated upregulation of ligand activity by Neuralized and inhibition of receptor activity by Numb results in a robust bias in Notch signaling. ..
- Herz H, Woodfield S, Chen Z, Bolduc C, Bergmann A. Common and distinct genetic properties of ESCRT-II components in Drosophila. PLoS ONE. 2009;4:e4165 pubmed publisher..Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation. ..
- Harris K, Tepass U. Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis. J Cell Biol. 2008;183:1129-43 pubmed publisher..This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs. ..
- Giebel B, Wodarz A. Tumor suppressors: control of signaling by endocytosis. Curr Biol. 2006;16:R91-2 pubmed..These results can be attributed to defective endocytosis of transmembrane proteins that control cell polarity and proliferation, including Crumbs and Notch. ..
- Satoh A, O Tousa J, Ozaki K, Ready D. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development. 2005;132:1487-97 pubmed..These results establish a role for Rab11 in the post-Golgi transport of rhodopsin and of other proteins to the rhabdomeric membranes of photoreceptors, and in analogous transport processes in other cells. ..
- Seto E, Bellen H. Internalization is required for proper Wingless signaling in Drosophila melanogaster. J Cell Biol. 2006;173:95-106 pubmed..As these data indicate that endosomal transport promotes Wg signaling, our findings suggest that the regulation of endocytosis is a novel mechanism through which Wg signaling levels are determined. ..
- Williamson W, Wang D, Haberman A, Hiesinger P. A dual function of V0-ATPase a1 provides an endolysosomal degradation mechanism in Drosophila melanogaster photoreceptors. J Cell Biol. 2010;189:885-99 pubmed publisher..We propose that V100 exerts a temporally integrated dual function that increases neuronal degradative capacity. ..
- Politi Y, Gal L, Kalifa Y, Ravid L, Elazar Z, Arama E. Paternal mitochondrial destruction after fertilization is mediated by a common endocytic and autophagic pathway in Drosophila. Dev Cell. 2014;29:305-20 pubmed publisher..Finally, we show that the ubiquitin ligase Parkin is not involved in PMD, implying a divergence from the autophagic pathway of damaged mitochondria. ..
- Khadilkar R, Rodrigues D, Mote R, Sinha A, Kulkarni V, Magadi S, et al. ARF1-GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis. Proc Natl Acad Sci U S A. 2014;111:4898-903 pubmed publisher..We propose that the conserved ARF1-Asrij endocytic axis modulates signals that govern hematopoietic development. Thus, Asrij affords tissue-specific control of global mechanisms involved in molecular traffic. ..
- Lee G, Liang C, Park G, Jang C, Jung J, Chung J. UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila. Dev Biol. 2011;356:588-97 pubmed publisher..Consistently, UVRAG-mutated heterotaxy patient cells also display highly increased Notch protein levels. These results suggest evolutionarily conserved roles of UVRAG in organ rotation by regulating Notch endocytic degradation. ..
- Sheng Z, Yu L, Zhang T, Pei X, Li X, Zhang Z, et al. ESCRT-0 complex modulates Rbf-mutant cell survival by regulating Rhomboid endosomal trafficking and EGFR signaling. J Cell Sci. 2016;129:2075-84 pubmed publisher..we identified synthetic lethal interactions between mutations of fly Rb (rbf) and the ESCRT-0 components stam and hrs We show that inactivation of ESCRT-0 sensitizes rbf-mutant cells to undergo apoptosis through inhibition of EGFR ..
- Haberman A, Akbar M, Ray S, KRAMER H. Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking. Development. 2010;137:2157-66 pubmed publisher..Taken together, our data show that dacn encodes a regulator of endosomal and autophagosomal dynamics, modulating developmental signaling and the cellular response to starvation. ..
- Stahelin R, Long F, Diraviyam K, Bruzik K, Murray D, Cho W. Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs. J Biol Chem. 2002;277:26379-88 pubmed
- Lee Y, Pressman S, Andress A, Kim K, White J, Cassidy J, et al. Silencing by small RNAs is linked to endosomal trafficking. Nat Cell Biol. 2009;11:1150-6 pubmed publisher..It may provide a means to enhance the dynamics of RNA silencing in the cytoplasm. ..
- Cho K, Kim G, Lee O. Wolbachia bacteria reside in host Golgi-related vesicles whose position is regulated by polarity proteins. PLoS ONE. 2011;6:e22703 pubmed publisher..Thus, establishment of polarity may be closely linked to the precise insertion of Golgi vesicles into the new membrane addition site. ..
- Richardson E, Pichaud F. Crumbs is required to achieve proper organ size control during Drosophila head development. Development. 2010;137:641-50 pubmed publisher..Overall, our work reveals a novel function for Crb in limiting ligand-dependent transactivation of the N receptor at the epithelial cell membrane. ..
- Daskalaki A, Shalaby N, Kux K, Tsoumpekos G, Tsibidis G, Muskavitch M, et al. Distinct intracellular motifs of Delta mediate its ubiquitylation and activation by Mindbomb1 and Neuralized. J Cell Biol. 2011;195:1017-31 pubmed publisher..We found an excellent correlation between the ability to undergo ubiquitylation and signaling. Therefore, ubiquitylation of the DSL ICD seems to be a necessary step in the activation of Notch. ..
- Bianco A, Poukkula M, Cliffe A, Mathieu J, Luque C, Fulga T, et al. Two distinct modes of guidance signalling during collective migration of border cells. Nature. 2007;448:362-5 pubmed..Thus, information processing at the multicellular level is used to guide collective behaviour of a cell group. ..
- Loncle N, Agromayor M, Martin Serrano J, Williams D. An ESCRT module is required for neuron pruning. Sci Rep. 2015;5:8461 pubmed publisher..Furthermore we show that this ESCRT module requires a direct, in vivo, interaction between Shrub/CHMP4B and the accessory protein Myopic/HD-PTP. ..
- Rodahl L, Haglund K, Sem Jacobsen C, Wendler F, Vincent J, Lindmo K, et al. Disruption of Vps4 and JNK function in Drosophila causes tumour growth. PLoS ONE. 2009;4:e4354 pubmed publisher..We conclude that dvps4 is a tumour suppressor in Drosophila and that JNK is central to the cell-autonomous phenotypes of ESCRT-deficient cells. ..
- Li X, Kuromi H, Briggs L, Green D, Rocha J, Sweeney S, et al. Bicaudal-D binds clathrin heavy chain to promote its transport and augments synaptic vesicle recycling. EMBO J. 2010;29:992-1006 pubmed publisher..Our results implicate BicD as a new player in clathrin-associated trafficking processes and show a novel requirement for microtubule-based motor transport in the synaptic vesicle cycle. ..
- Nagaraj R, Banerjee U. Regulation of Notch and Wingless signalling by phyllopod, a transcriptional target of the EGFR pathway. EMBO J. 2009;28:337-46 pubmed publisher..Furthermore, this study identifies a Phyl-regulated class of endosomal vesicles that specifically include components of Notch and Wg signalling. ..
- Legent K, Liu H, Treisman J. Drosophila Vps4 promotes Epidermal growth factor receptor signaling independently of its role in receptor degradation. Development. 2015;142:1480-91 pubmed publisher..Taken together, these findings indicate that Vps4 can promote EGFR activity through an endocytosis-independent mechanism. ..
- Fan J, Jiang K, Liu Y, Jia J. Hrs promotes ubiquitination and mediates endosomal trafficking of smoothened in Drosophila hedgehog signaling. PLoS ONE. 2013;8:e79021 pubmed publisher..Here, we demonstrate that inactivation of Hrs by deletion or RNAi accumulates Smo in the late endosome that is marked by late endosome markers...
- Hartenstein K, Sinha P, Mishra A, Schenkel H, Torok I, Mechler B. The congested-like tracheae gene of Drosophila melanogaster encodes a member of the mitochondrial carrier family required for gas-filling of the tracheal system and expansion of the wings after eclosion. Genetics. 1997;147:1755-68 pubmed
- Mao Y, Nickitenko A, Duan X, Lloyd T, Wu M, Bellen H, et al. Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction. Cell. 2000;100:447-56 pubmed..have determined the 2 A X-ray structure of the 219-residue N-terminal VHS and FYVE tandem domain unit of Drosophila Hrs. The unit assumes a pyramidal structure in which the much larger VHS domain (residues 1-153) forms a rectangular ..
- Liu Z, Huang Y, Zhang Y, Chen D, Zhang Y. Drosophila Acyl-CoA synthetase long-chain family member 4 regulates axonal transport of synaptic vesicles and is required for synaptic development and transmission. J Neurosci. 2011;31:2052-63 pubmed publisher..marker lysosome-associated membrane protein 1, the autophagosomal marker Atg8, and the multivesicular body marker Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate)...
- Wu J, Bakerink K, Evangelista M, Thomas G. Cytoplasmic capes are nuclear envelope intrusions that are enriched in endosomal proteins and depend upon ?H-spectrin and Annexin B9. PLoS ONE. 2014;9:e93680 pubmed publisher..Diminution of these structures does not lead to a change in mSpitz processing. These results extend the endosomal influence of ?H and its partner Annexin B9 to this unusual compartment at the nuclear envelope. ..
- Xu H, Mohtashami M, Stewart B, Boulianne G, Trimble W. Drosophila SNAP-29 is an essential SNARE that binds multiple proteins involved in membrane traffic. PLoS ONE. 2014;9:e91471 pubmed publisher..Overexpression and RNAi studies suggested that dSNAP-29 mediates an essential process in Drosophila development. ..
- Powis K, MacDougall L. The localisation of PtdIns3P in Drosophila fat responds to nutrients but not insulin: a role for Class III but not Class II phosphoinositide 3-kinases. Cell Signal. 2011;23:1153-61 pubmed publisher..We find that both Class II and Class III PI3Ks are capable of generating PtdIns3P in vivo but the source of PtdIns3P in the fat body and the response to nutritional status can be exclusively accounted for by Class III PI3K activity. ..
- Gallagher C, Knoblich J. The conserved c2 domain protein lethal (2) giant discs regulates protein trafficking in Drosophila. Dev Cell. 2006;11:641-53 pubmed..These enlarged endosomes are positive for Rab5 and Hrs, a protein involved in trafficking into the degradative pathway...
- Belenkaya T, Wu Y, Tang X, Zhou B, Cheng L, Sharma Y, et al. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Dev Cell. 2008;14:120-31 pubmed..Our findings link Wls and retromer functions in the same conserved Wnt secretion pathway. We propose that retromer influences Wnt secretion by recycling Wntless from endosomes to the trans-Golgi network (TGN). ..
- Morawa K, Schneider M, Klein T. Lgd regulates the activity of the BMP/Dpp signalling pathway during Drosophila oogenesis. Development. 2015;142:1325-35 pubmed publisher..They further show that there is a role for the endosomal pathway during oogenesis. ..