Daniela Rotin

Summary

Affiliation: The Hospital for Sick Children
Country: Canada

Publications

  1. pmc Nedd4-2 and the regulation of epithelial sodium transport
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto Toronto, ON, Canada
    Front Physiol 3:212. 2012
  2. pmc A splice isoform of DNedd4, DNedd4-long, negatively regulates neuromuscular synaptogenesis and viability in Drosophila
    Yunan Zhong
    Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada
    PLoS ONE 6:e27007. 2011
  3. pmc A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteins
    Ruth Milkereit
    Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 6:e27478. 2011
  4. pmc Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeast
    Ronish Gupta
    Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Mol Syst Biol 3:116. 2007
  5. pmc Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination
    Youngshil Pak
    Program in Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, M5G 1X8
    J Cell Biol 175:631-45. 2006
  6. pmc Neural stem cells from protein tyrosine phosphatase sigma knockout mice generate an altered neuronal phenotype in culture
    David L Kirkham
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton Ontario, L8N 3Z5, Canada
    BMC Neurosci 7:50. 2006
  7. ncbi request reprint Physiological functions of the HECT family of ubiquitin ligases
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, Ontario, Canada
    Nat Rev Mol Cell Biol 10:398-409. 2009
  8. pmc Role of the UPS in Liddle syndrome
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Ontario, M5G 1X8, Canada
    BMC Biochem 9:S5. 2008
  9. doi request reprint Role of the ubiquitin system in regulating ion transport
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children and Biochemistry Department, University of Toronto, Toronto, Canada
    Pflugers Arch 461:1-21. 2011
  10. ncbi request reprint ENaC and its regulatory proteins as drug targets for blood pressure control
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, TMDT MaRS, Rm 11 305, 101 College St, Toronto, Ont, Canada
    Curr Drug Targets 9:709-16. 2008

Collaborators

Detail Information

Publications46

  1. pmc Nedd4-2 and the regulation of epithelial sodium transport
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto Toronto, ON, Canada
    Front Physiol 3:212. 2012
    ..Collectively, these new findings underscore the physiological importance of Nedd4-2 in regulating epithelial salt and fluid transport and balance...
  2. pmc A splice isoform of DNedd4, DNedd4-long, negatively regulates neuromuscular synaptogenesis and viability in Drosophila
    Yunan Zhong
    Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada
    PLoS ONE 6:e27007. 2011
    ..DNedd4 is an E3 ubiquitin ligase comprised of a C2-WW(x3)-Hect domain architecture, which includes several splice isoforms, the most prominent ones are dNedd4-short (dNedd4S) and dNedd4-long (dNedd4Lo)...
  3. pmc A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteins
    Ruth Milkereit
    Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 6:e27478. 2011
    ..While we had demonstrated earlier the requirement of the E3 ubiquitin ligase Nedd4 for LAPTM5 sorting to lysosomes, the regulation of sorting of LAPTM4 proteins is less clear...
  4. pmc Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeast
    Ronish Gupta
    Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    Mol Syst Biol 3:116. 2007
    ..The development of a platform for global discovery of E3 substrates is invaluable for understanding the cellular pathways in which they participate, and could be utilized for the identification of drug targets...
  5. pmc Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination
    Youngshil Pak
    Program in Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, M5G 1X8
    J Cell Biol 175:631-45. 2006
    ..These results demonstrate a novel mechanism by which the ubiquitin-ligase Nedd4, via interactions with GGA3 and cargo (LAPTM5), regulates cargo trafficking to the lysosome without requiring cargo ubiquitination...
  6. pmc Neural stem cells from protein tyrosine phosphatase sigma knockout mice generate an altered neuronal phenotype in culture
    David L Kirkham
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton Ontario, L8N 3Z5, Canada
    BMC Neurosci 7:50. 2006
    ....
  7. ncbi request reprint Physiological functions of the HECT family of ubiquitin ligases
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, Ontario, Canada
    Nat Rev Mol Cell Biol 10:398-409. 2009
    ..The physiological functions of the yeast HECT E3 ligase Rsp5 are the best known, but the functions of HECT E3 enyzmes in metazoans are now becoming clearer from in vivo studies...
  8. pmc Role of the UPS in Liddle syndrome
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Ontario, M5G 1X8, Canada
    BMC Biochem 9:S5. 2008
    ..PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com)...
  9. doi request reprint Role of the ubiquitin system in regulating ion transport
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children and Biochemistry Department, University of Toronto, Toronto, Canada
    Pflugers Arch 461:1-21. 2011
    ..We also briefly discuss the role of ubiquitin like molecules (such as SUMO) in such regulation, for which much less is known so far...
  10. ncbi request reprint ENaC and its regulatory proteins as drug targets for blood pressure control
    Daniela Rotin
    Program in Cell Biology, The Hospital for Sick Children, TMDT MaRS, Rm 11 305, 101 College St, Toronto, Ont, Canada
    Curr Drug Targets 9:709-16. 2008
    ....
  11. pmc Regulation of Commissureless by the ubiquitin ligase DNedd4 is required for neuromuscular synaptogenesis in Drosophila melanogaster
    Bryant Ing
    The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
    Mol Cell Biol 27:481-96. 2007
    ..These results demonstrate that dNedd4 and ubiquitination are required for Commissureless endocytosis and proper neuromuscular synaptogenesis...
  12. ncbi request reprint The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool
    Chen Lu
    Program in Cell Biology, The Hospital for Sick Children, Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 1X8
    Traffic 8:1246-64. 2007
    ..These results suggest that the ENaC PY motifs (and Nedd4-2) primarily regulate channel internalization but also affect cAMP-dependent replenishment, providing important insight into the Liddle syndrome defects...
  13. pmc Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function
    Avinash Persaud
    Programs in Cell Biology and Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    EMBO J 30:3259-73. 2011
    ..These results identify Nedd4-1 as a key regulator of FGFR1 endocytosis and signalling during neuronal differentiation and embryonic development...
  14. pmc Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays
    Avinash Persaud
    Programs in Cell Biology and Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada
    Mol Syst Biol 5:333. 2009
    ..g. FGFR), suggesting Nedd4-1 suppresses their signalling. These results demonstrate the feasibility of identifying substrates and deciphering substrate specificity of mammalian E3 ligases...
  15. ncbi request reprint Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain
    M Christine Bruce
    Program in Cell and Structure Biology, The Hospital for Sick Children, University of Toronto, 101 College Street, Toronto, ON, Canada, M5G 1L7
    Biochem J 415:155-63. 2008
    ..These findings also point to a novel mechanism employed by a ubiquitin ligase to regulate itself differentially compared with substrate ubiquitination and stability...
  16. pmc Use of kinase inhibitors to correct ΔF508-CFTR function
    Agata M Trzcinska-Daneluti
    Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1L7
    Mol Cell Proteomics 11:745-57. 2012
    ....
  17. ncbi request reprint Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex
    Voula Kanelis
    Programme in Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    Structure 14:543-53. 2006
    ..In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development...
  18. ncbi request reprint Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain
    Silke Wiesner
    Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    Cell 130:651-62. 2007
    ..Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells...
  19. ncbi request reprint Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel
    Pauline C Henry
    Programme in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    J Biol Chem 278:20019-28. 2003
    ..Collectively, these results suggest that high affinity of WW domain-PY-motif interactions rather than affiliation with Nedd4-1/Nedd-2 is critical for ENaC suppression by Nedd4 proteins...
  20. ncbi request reprint Apparent normal lung architecture in protein tyrosine phosphatase-sigma-deficient mice
    Jane Batt
    Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
    Am J Physiol Lung Cell Mol Physiol 284:L214-23. 2003
    ..These observations suggest compensation for the absence of PTP-sigma during development by related family member phosphatases, such as LAR...
  21. pmc High-content functional screen to identify proteins that correct F508del-CFTR function
    Agata M Trzcinska-Daneluti
    Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, Ontario M5G 1L7, Canada
    Mol Cell Proteomics 8:780-90. 2009
    ..This assay can also be utilized for RNAi screens to identify inhibitory proteins that block correction of F508del-CFTR, small molecule, and peptide screens...
  22. ncbi request reprint Interactions between the three CIN85 SH3 domains and ubiquitin: implications for CIN85 ubiquitination
    Irina Bezsonova
    Department of Chemistry, University of Toronto, 80 St George Street, Toronto, ON, Canada M5S 1A8
    Biochemistry 47:8937-49. 2008
    ..These results suggest that competition between Cbl and ubiquitin binding to CIN85 regulates Cbl function and EGFR endocytosis...
  23. pmc The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1
    Fatemeh Fouladkou
    Program in Cell Biology and the Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 285:6770-80. 2010
    ..These results suggest that Nedd4-1 is a suppressor of Tsp1 and that increased levels of Tsp-1 in the Nedd4-1 knock-out mice may have contributed to the developmental defect observed in the embryos...
  24. ncbi request reprint The guanine nucleotide exchange factor CNrasGEF regulates melanogenesis and cell survival in melanoma cells
    Eva M Amsen
    Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    J Biol Chem 281:121-8. 2006
    ..Collectively, these results suggest that CNrasGEF regulates melanogenesis but that it also has a distinct role in regulating cell proliferation/apoptosis...
  25. ncbi request reprint Protein tyrosine phosphatase sigma-deficient mice show aberrant cytoarchitecture and structural abnormalities in the central nervous system
    Karen Meathrel
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
    J Neurosci Res 70:24-35. 2002
    ..These data suggest that PTPsigma is likely involved in neurogenesis, axonal growth, and axonal pathfinding in the maturation of the mammalian CNS...
  26. pmc Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation
    Youngshil Pak
    Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, M5G 1X8 Ontario, Canada
    Mol Cell Biol 22:7942-52. 2002
    ..The present study provides the first demonstration of direct physical association between a Ras activator and a GPCR, leading to agonist-induced Ras activation..
  27. pmc Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease
    Toshihiro Kimura
    Departments of Biochemistry and Physiology, The Hospital for Sick Children, Programs in Cell Biology and Neuroscience and Mental Health, and University of Toronto, Toronto, ON, Canada M5G 1X8
    Proc Natl Acad Sci U S A 108:3216-21. 2011
    ..Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia...
  28. pmc The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
    Fatemeh Fouladkou
    Hospital for Sick Children and Biochemistry Department, University of Toronto, MaRS TMDT, 101 College Street, Toronto, Ontario M5G 1L7, Canada
    Proc Natl Acad Sci U S A 105:8585-90. 2008
    ..Taken together, our results fail to support a role for Nedd4-1 as the E3 ligase regulating PTEN stability and subcellular localization...
  29. pmc LAPTM5 protein is a positive regulator of proinflammatory signaling pathways in macrophages
    Wioletta K Glowacka
    Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, Ontario M5G 1L7, Canada
    J Biol Chem 287:27691-702. 2012
    ..They also highlight a role for the endosomal/lysosomal system in regulating signaling via cytokine and pattern recognition receptors...
  30. ncbi request reprint Enhanced rate of nerve regeneration and directional errors after sciatic nerve injury in receptor protein tyrosine phosphatase sigma knock-out mice
    Joanna McLean
    Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, M5G 1X8
    J Neurosci 22:5481-91. 2002
    ..We propose that PTPsigma regulates the axonal regeneration rate and guidance of regenerating fibers...
  31. doi request reprint Use of proteome arrays to globally identify substrates for E3 ubiquitin ligases
    Avinash Persaud
    Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada
    Methods Mol Biol 759:215-24. 2011
    ..The in vitro ubiquitylation and binding substrates identified in these screens can provide invaluable insight into the cellular pathways in which E3 ligases participate...
  32. pmc Protein tyrosine phosphatase σ targets apical junction complex proteins in the intestine and regulates epithelial permeability
    Ryan Murchie
    Program in Cell Biology and Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada, M5G 1X8
    Proc Natl Acad Sci U S A 111:693-8. 2014
    ....
  33. pmc A strategy for modulation of enzymes in the ubiquitin system
    Andreas Ernst
    Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada
    Science 339:590-5. 2013
    ..Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system...
  34. doi request reprint Functional rescue of DeltaF508-CFTR by peptides designed to mimic sorting motifs
    Patrick Kim Chiaw
    Research Institute, Hospital for Sick Children, University of Toronto, ON, Canada
    Chem Biol 16:520-30. 2009
    ....
  35. pmc N-cadherin is an in vivo substrate for protein tyrosine phosphatase sigma (PTPsigma) and participates in PTPsigma-mediated inhibition of axon growth
    Roberta Siu
    Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto M5G 1X8, Ontario, Canada
    Mol Cell Biol 27:208-19. 2007
    ..We conclude that N-cadherin is a physiological substrate for PTPsigma and that N-cadherin (and likely beta-catenin) participates in PTPsigma-mediated inhibition of axon growth...
  36. pmc The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice
    Preena Nagpal
    Keenan Research Centre of the LiKaShing Knowledge Institute, St Michaels Hospital, Toronto, Ontario, Canada
    PLoS ONE 7:e46427. 2012
    ..These effects are not mediated by the Nedd4-1 substrates MTMR4, FGFR1 and Notch-1. These results demonstrate that Nedd4-1 plays an important role in mediating denervation-induced skeletal muscle atrophy in vivo...
  37. pmc Regulation of lipid droplet turnover by ubiquitin ligases
    Philipp Alberts
    Cell Biology Program, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, Ontario, M5G 1L7, Canada
    BMC Biol 8:94. 2010
    ..A deficiency of spartin apparently causes lipid droplets to accumulate...
  38. ncbi request reprint Protein-tyrosine phosphatase sigma is associated with ulcerative colitis
    Aleixo M Muise
    Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, 555 University Ave, Toronto, Ontario, Canada
    Curr Biol 17:1212-8. 2007
    ..We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis...
  39. ncbi request reprint Pituitary, pancreatic and gut neuroendocrine defects in protein tyrosine phosphatase-sigma-deficient mice
    Jane Batt
    The Hospital for Sick Children, Program in Cell Biology, and Institute of Medical Science and Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1X8, Canada
    Mol Endocrinol 16:155-69. 2002
    ..These data indicate that PTPfinal sigma plays a major role in differentiation and development of the neuroendocrine system...
  40. ncbi request reprint A high throughput screen to identify substrates for the ubiquitin ligase Rsp5
    Bart Kus
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    J Biol Chem 280:29470-8. 2005
    ..The combination of this sensitive assay and the availability of purified substrates will enable the identification of substrates for any purified E3 enzyme...
  41. ncbi request reprint Trafficking and cell surface stability of the epithelial Na+ channel expressed in epithelial Madin-Darby canine kidney cells
    David Hanwell
    Hospital for Sick Children and the Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1X8, Canada
    J Biol Chem 277:9772-9. 2002
    ..Collectively, these results help elucidate key aspects of ENaC trafficking and turnover rates in mammalian kidney epithelial cells...
  42. doi request reprint Apical junction complex proteins and ulcerative colitis: a focus on the PTPRS gene
    Aleixo Muise
    Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
    Expert Rev Mol Diagn 8:465-77. 2008
    ..We will focus on the PTPRS (encoding PTPsigma) gene and discuss its and other apical junction complex proteins' role in the pathogenesis of UC...
  43. ncbi request reprint Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor
    Anna Myat
    Molecular Neurobiology Group, MRC Centre for Developmental Neurobiology, King s College London, New Hunt s House, Guy s Campus, London SE1 1UL, United Kingdom
    Neuron 35:447-59. 2002
    ..Our results show that changes in axonal sensitivity to external cues during pathfinding across the midline makes use of ubiquitin-dependent mechanisms to regulate transmembrane protein levels...
  44. ncbi request reprint Regulation of the epithelial Na+ channel by cytosolic ATP
    Toru Ishikawa
    Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060 0818, Japan
    J Biol Chem 278:38276-86. 2003
    ..We propose that this novel ATP regulation of ENaC may be, at least in part, involved in the fine-tuning of ENaC activity under physiologic and pathophysiologic conditions...
  45. ncbi request reprint Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins
    Jean Sebastien Rougier
    Department of Pharmacology and Toxicology, Service of Cardiology, University of Lausanne, Rue du Bugnon 27, CH 1005 Lausanne, Switzerland
    Am J Physiol Cell Physiol 288:C692-701. 2005
    ..This study shows that Nedd4-dependent ubiquitination of Na(v) channels may represent a general mechanism regulating the excitability of neurons and myocytes via modulation of channel density at the plasma membrane...
  46. pmc The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor
    Andrea Vecchione
    Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Cell Biol 23:3363-72. 2003
    ..This is the first demonstration of regulation of stability of a tyrosine kinase receptor by the Nedd4 (HECT) family of E3 ligases...