Todd Graham
Last active: 12/3/2018

Profile

The research goals of the Graham laboratory are to understand the molecular mechanisms underpinning vesicle-mediated protein transport and membrane biogenesis. One focal area is determining how type IV P-type ATPases (P4-ATPases) catalyze phospholipid flippase activity and contribute to the establishment of membrane asymmetry. This process is important for signal transduction, regulation of apoptosis and blood clotting, cytokinesis and vesicular transport. P4-ATPase deficiency is linked to diet-induced obesity, type 2 diabetes, liver disease, immune deficiency, hearing loss and neurodegenerative disease. A second focal area is to define mechanisms of protein trafficking between the Golgi, cell surface and endosomal system with an emphasis on the role of coat proteins, SNAREs, and protein ubiquitylation. These trafficking pathways play important roles in metabolism, cancer cell biology and neuronal function.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal. Xu P, Hankins HM, MacDonald C, Erlinger SJ, Frazier MN, Diab NS, Piper RC, Jackson LP, MacGurn JA, Graham TR (2017) Elife
    › Primary publication · 29058666 (PubMed) · PMC5663479 (PubMed Central)
  2. Exploring genetic suppression interactions on a global scale. van Leeuwen J, Pons C, Mellor JC, Yamaguchi TN, Friesen H, Koschwanez J, Ušaj MM, Pechlaner M, Takar M, Ušaj M, VanderSluis B, Andrusiak K, Bansal P, Baryshnikova A, Boone CE, Cao J, Cote A, Gebbia M, Horecka G, Horecka I, Kuzmin E, Legro N, Liang W, van Lieshout N, McNee M, San Luis BJ, Shaeri F, Shuteriqi E, Sun S, Yang L, Youn JY, Yuen M, Costanzo M, Gingras AC, Aloy P, Oostenbrink C, Murray A, Graham TR, Myers CL, Andrews BJ, Roth FP, Boone C (2016) Science 354(6312)
    › Primary publication · 27811238 (PubMed) · PMC5562937 (PubMed Central)
  3. Neo1 and phosphatidylethanolamine contribute to vacuole membrane fusion in . Wu Y, Takar M, Cuentas-Condori AA, Graham TR (2016) Cell Logist 6(3): e1228791
    › Primary publication · 27738552 (PubMed) · PMC5058351 (PubMed Central)
  4. Decoding P4-ATPase substrate interactions. Roland BP, Graham TR (2016) Crit Rev Biochem Mol Biol 51(6): 513-527
    › Primary publication · 27696908 (PubMed) · PMC5285478 (PubMed Central)
  5. Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase. Roland BP, Graham TR (2016) Proc Natl Acad Sci U S A 113(31): E4460-6
    › Primary publication · 27432949 (PubMed) · PMC4978280 (PubMed Central)
  6. The Essential Neo1 Protein from Budding Yeast Plays a Role in Establishing Aminophospholipid Asymmetry of the Plasma Membrane. Takar M, Wu Y, Graham TR (2016) J Biol Chem 291(30): 15727-39
    › Primary publication · 27235400 (PubMed) · PMC4957055 (PubMed Central)
  7. Phosphatidylserine translocation at the yeast trans-Golgi network regulates protein sorting into exocytic vesicles. Hankins HM, Sere YY, Diab NS, Menon AK, Graham TR (2015) Mol Biol Cell 26(25): 4674-85
    › Primary publication · 26466678 (PubMed) · PMC4678023 (PubMed Central)
  8. Role of flippases, scramblases and transfer proteins in phosphatidylserine subcellular distribution. Hankins HM, Baldridge RD, Xu P, Graham TR (2015) Traffic 16(1): 35-47
    › Primary publication · 25284293 (PubMed) · PMC4275391 (PubMed Central)
  9. Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl-terminal tail. Zhou X, Sebastian TT, Graham TR (2013) J Biol Chem 288(44): 31807-15
    › Primary publication · 24045945 (PubMed) · PMC3814774 (PubMed Central)
  10. Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport. Xu P, Baldridge RD, Chi RJ, Burd CG, Graham TR (2013) J Cell Biol 202(6): 875-86
    › Primary publication · 24019533 (PubMed) · PMC3776346 (PubMed Central)
  11. Type IV P-type ATPases distinguish mono- versus diacyl phosphatidylserine using a cytofacial exit gate in the membrane domain. Baldridge RD, Xu P, Graham TR (2013) J Biol Chem 288(27): 19516-27
    › Primary publication · 23709217 (PubMed) · PMC3707653 (PubMed Central)
  12. Arl1 gets into the membrane remodeling business with a flippase and ArfGEF. Graham TR (2013) Proc Natl Acad Sci U S A 110(8): 2691-2
    › Primary publication · 23401560 (PubMed) · PMC3581979 (PubMed Central)
  13. Two-gate mechanism for phospholipid selection and transport by type IV P-type ATPases. Baldridge RD, Graham TR (2013) Proc Natl Acad Sci U S A 110(5): E358-67
    › Primary publication · 23302692 (PubMed) · PMC3562821 (PubMed Central)
  14. Identification of residues defining phospholipid flippase substrate specificity of type IV P-type ATPases. Baldridge RD, Graham TR (2012) Proc Natl Acad Sci U S A 109(6): E290-8
    › Primary publication · 22308393 (PubMed) · PMC3277569 (PubMed Central)
  15. Phospholipid flippases: building asymmetric membranes and transport vesicles. Sebastian TT, Baldridge RD, Xu P, Graham TR (2012) Biochim Biophys Acta 1821(8): 1068-77
    › Primary publication · 22234261 (PubMed) · PMC3368091 (PubMed Central)
  16. Coordination of Golgi functions by phosphatidylinositol 4-kinases. Graham TR, Burd CG (2011) Trends Cell Biol 21(2): 113-21
    › Primary publication · 21282087 (PubMed) · PMC3053015 (PubMed Central)
  17. Interplay of proteins and lipids in generating membrane curvature. Graham TR, Kozlov MM (2010) Curr Opin Cell Biol 22(4): 430-6
    › Primary publication · 20605711 (PubMed) · PMC3770468 (PubMed Central)
  18. Regulation of a Golgi flippase by phosphoinositides and an ArfGEF. Natarajan P, Liu K, Patil DV, Sciorra VA, Jackson CL, Graham TR (2009) Nat Cell Biol 11(12): 1421-6
    › Primary publication · 19898464 (PubMed) · PMC2787759 (PubMed Central)
  19. Reconstitution of phospholipid translocase activity with purified Drs2p, a type-IV P-type ATPase from budding yeast. Zhou X, Graham TR (2009) Proc Natl Acad Sci U S A 106(39): 16586-91
    › Primary publication · 19805341 (PubMed) · PMC2757829 (PubMed Central)
  20. Control of protein and sterol trafficking by antagonistic activities of a type IV P-type ATPase and oxysterol binding protein homologue. Muthusamy BP, Raychaudhuri S, Natarajan P, Abe F, Liu K, Prinz WA, Graham TR (2009) Mol Biol Cell 20(12): 2920-31
    › Primary publication · 19403696 (PubMed) · PMC2695799 (PubMed Central)
  21. Linking phospholipid flippases to vesicle-mediated protein transport. Muthusamy BP, Natarajan P, Zhou X, Graham TR (2009) Biochim Biophys Acta 1791(7): 612-9
    › Primary publication · 19286470 (PubMed) · PMC3770137 (PubMed Central)
  22. P4-ATPase requirement for AP-1/clathrin function in protein transport from the trans-Golgi network and early endosomes. Liu K, Surendhran K, Nothwehr SF, Graham TR (2008) Mol Biol Cell 19(8): 3526-35
    › Primary publication · 18508916 (PubMed) · PMC2488278 (PubMed Central)
  23. Metabolic labeling and immunoprecipitation of yeast proteins. Graham TR (2001) Curr Protoc Cell Biol : Unit 7.6
    › Primary publication · 18228384 (PubMed)
  24. Yeast P4-ATPases Drs2p and Dnf1p are essential cargos of the NPFXD/Sla1p endocytic pathway. Liu K, Hua Z, Nepute JA, Graham TR (2007) Mol Biol Cell 18(2): 487-500
    › Primary publication · 17122361 (PubMed) · PMC1783782 (PubMed Central)
  25. Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane. Chen S, Wang J, Muthusamy BP, Liu K, Zare S, Andersen RJ, Graham TR (2006) Traffic 7(11): 1503-17
    › Primary publication · 16956384 (PubMed)
  26. Measuring translocation of fluorescent lipid derivatives across yeast Golgi membranes. Natarajan P, Graham TR (2006) Methods 39(2): 163-8
    › Primary publication · 16828307 (PubMed)
  27. Dissection of Swa2p/auxilin domain requirements for cochaperoning Hsp70 clathrin-uncoating activity in vivo. Xiao J, Kim LS, Graham TR (2006) Mol Biol Cell 17(7): 3281-90
    › Primary publication · 16687570 (PubMed) · PMC1483056 (PubMed Central)
  28. Flippases and vesicle-mediated protein transport. Graham TR (2004) Trends Cell Biol 14(12): 670-7
    › Primary publication · 15564043 (PubMed)
  29. Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. Natarajan P, Wang J, Hua Z, Graham TR (2004) Proc Natl Acad Sci U S A 101(29): 10614-9
    › Primary publication · 15249668 (PubMed) · PMC489982 (PubMed Central)
  30. Membrane targeting: getting Arl to the Golgi. Graham TR (2004) Curr Biol 14(12): R483-5
    › Primary publication · 15203023 (PubMed)
  31. Solution structure of the ubiquitin-binding domain in Swa2p from Saccharomyces cerevisiae. Chim N, Gall WE, Xiao J, Harris MP, Graham TR, Krezel AM (2004) Proteins 54(4): 784-93
    › Primary publication · 14997574 (PubMed)
  32. Requirement for neo1p in retrograde transport from the Golgi complex to the endoplasmic reticulum. Hua Z, Graham TR (2003) Mol Biol Cell 14(12): 4971-83
    › Primary publication · 12960419 (PubMed) · PMC284799 (PubMed Central)
  33. Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. Gall WE, Geething NC, Hua Z, Ingram MF, Liu K, Chen SI, Graham TR (2002) Curr Biol 12(18): 1623-7
    › Primary publication · 12372257 (PubMed)
  34. An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/vacuolar system. Hua Z, Fatheddin P, Graham TR (2002) Mol Biol Cell 13(9): 3162-77
    › Primary publication · 12221123 (PubMed) · PMC124150 (PubMed Central)
  35. The auxilin-like phosphoprotein Swa2p is required for clathrin function in yeast. Gall WE, Higginbotham MA, Chen C, Ingram MF, Cyr DM, Graham TR (2000) Curr Biol 10(21): 1349-58
    › Primary publication · 11084334 (PubMed)
  36. Introduction of Kex2 cleavage sites in fusion proteins for monitoring localization and transport in yeast secretory pathway. Hopkins BD, Sato K, Nakano A, Graham TR (2000) Methods Enzymol : 107-18
    › Primary publication · 11044978 (PubMed)
  37. Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. Chen CY, Ingram MF, Rosal PH, Graham TR (1999) J Cell Biol 147(6): 1223-36
    › Primary publication · 10601336 (PubMed) · PMC2168089 (PubMed Central)
  38. The high osmolarity glycerol response (HOG) MAP kinase pathway controls localization of a yeast golgi glycosyltransferase. Reynolds TB, Hopkins BD, Lyons MR, Graham TR (1998) J Cell Biol 143(4): 935-46
    › Primary publication · 9817752 (PubMed) · PMC2132948 (PubMed Central)
  39. An arf1Delta synthetic lethal screen identifies a new clathrin heavy chain conditional allele that perturbs vacuolar protein transport in Saccharomyces cerevisiae. Chen CY, Graham TR (1998) Genetics 150(2): 577-89
    › Primary publication · 9755191 (PubMed) · PMC1460353 (PubMed Central)
  40. Clathrin-dependent localization of alpha 1,3 mannosyltransferase to the Golgi complex of Saccharomyces cerevisiae. Graham TR, Seeger M, Payne GS, MacKay VL, Emr SD (1994) J Cell Biol 127(3): 667-78
    › Primary publication · 7962051 (PubMed) · PMC2120240 (PubMed Central)
  41. Sorting of yeast alpha 1,3 mannosyltransferase is mediated by a lumenal domain interaction, and a transmembrane domain signal that can confer clathrin-dependent Golgi localization to a secreted protein. Graham TR, Krasnov VA (1995) Mol Biol Cell 6(7): 809-24
    › Primary publication · 7579696 (PubMed) · PMC301242 (PubMed Central)