HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship

Human Molecular Genetics

Volumn 25, Issue 5, 2016, Pages 853-865

  Bode, Heiko ^a,b   Bourquin, Florence ^b   Suriyanarayanan, Saranya ^a,c   Wei, Yu ^a   Alecu, Irina ^a,b   Othman, Alaa ^a,c   Von Eckardstein, Arnold ^a,b,c   Hornemann, Thorsten ^a,b,c  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c Molecular Translation and Biomedicine ^*  (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; SERINE; SERINE PALMITOYLTRANSFERASE; SERINE PALMITOYLTRANSFERASE 1; SERINE PALMITOYLTRANSFERASE 2; SPHINGOSINE; UNCLASSIFIED DRUG; RECOMBINANT PROTEIN; SPHINGOLIPID; SPTLC1 PROTEIN, HUMAN; SPTLC2 PROTEIN, HUMAN;

ARTICLE; BIOCHEMICAL ANALYSIS; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; ENZYME ACTIVITY; GENE FUNCTION; GENE MUTATION; GENE STRUCTURE; GENETIC TRANSFECTION; GENETIC VARIABILITY; HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE 1; HUMAN; HUMAN CELL; ISOTOPE LABELING; OUTCOME ASSESSMENT; PERIPHERAL NEUROPATHY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN STRUCTURE; SITE DIRECTED MUTAGENESIS; SYNTHESIS; ADULT; AGED; BLOOD; CHEMISTRY; CHILD; ENZYME ACTIVE SITE; ENZYMOLOGY; GENE EXPRESSION; GENETICS; HEK293 CELL LINE; MASS FRAGMENTOGRAPHY; METABOLISM; MIDDLE AGED; MOLECULAR MODEL; MUTATION; NEUROPATHY; PATHOLOGY; PRINCIPAL COMPONENT ANALYSIS; SEVERITY OF ILLNESS INDEX; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; YOUNG ADULT;

ADULT; AGED; ALANINE; CATALYTIC DOMAIN; CHILD; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GENE EXPRESSION; HEK293 CELLS; HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES; HUMANS; ISOTOPE LABELING; MIDDLE AGED; MODELS, MOLECULAR; MUTATION; PHENOTYPE; PRINCIPAL COMPONENT ANALYSIS; RECOMBINANT PROTEINS; SERINE; SERINE C-PALMITOYLTRANSFERASE; SEVERITY OF ILLNESS INDEX; SPHINGOLIPIDS; STRUCTURAL HOMOLOGY, PROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP; YOUNG ADULT;

EID: 84962911328     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv611     Document Type: Article

References (66)

1. Dyck, P. J. (1993) Neuronal atrophy and degeneration predominantly affecting peripheral sensory and autonomic neurons. In Dyck, P.J., Thomas, K.P., Griffin, J.W., Low, P.A. and Poduslo, J.F. (eds), Peripheral Neuropathy, 3rd edn, Saunders, Philadelphia, pp. 1065-1093.
2. Edvardson, S., Cinnamon, Y., Jalas, C., Shaag, A., Maayan, C., Axelrod, F.B. and Elpeleg, O. (2012) Hereditary sensory autonomic neuropathy caused by a mutation in dystonin. Ann. Neurol., 71, 569-572.
3. Leipold, E., Liebmann, L., Korenke, G.C., Heinrich, T., Giesselmann, S., Baets, J., Ebbinghaus, M., Goral, R.O., Stödberg, T., Hennings, J.C. et al. (2013) A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nat. Genet., 45, 1399-1404.
4. Auer-Grumbach, M. (2008) Hereditary sensory neuropathy type I. Orphanet. J. Rare Dis., 3, 7-7.
5. Houlden, H., King, R., Blake, J. and Groves, M. (2006) Clinical, pathological and genetic characterization of hereditary sensory and autonomic neuropathy type 1 (HSAN I). Brain, 1, 411-425.
6. Denny-Brown, D.E. (1951) Hereditary sensory radicular neuropathy. J. Neurol. Neurosurg. Psychiatr., 14, 237-252.
7. Bejaoui, K., Wu, C., Scheffler, M.D., Haan, G., Ashby, P., Wu, L., de Jong, P. and Brown, R.H. (2001) SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat. Genet., 27, 261-262.
8. Dawkins, J.L., Hulme, D.J., Brahmbhatt, S.B., Auer-Grumbach, M. and Nicholson, G.A. (2001) Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat. Genet., 27, 309-312.
9. Rotthier, A., Auer-Grumbach, M., Janssens, K., Baets, J., Penno, A., Almeida-Souza, L., Van Hoof, K., Jacobs, A., De Vriendt, E., Schlotter-Weigel, B. et al. (2010) Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I. Am. J. Hum. Genet., 87, 513-522.
10. Guelly, C., Zhu, P.-P., Leonardis, L., Papić, L., Zidar, J., Schabhüttl, M., Strohmaier, H., Weis, J., Strom, T.M., Baets, J. et al. (2011) Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I. Am. J. Hum. Genet., 88, 99-105.
11. Klein, C.J., Botuyan, M.V., Wu, Y., Ward, C.J., Nicholson, G.A., Hammans, S., Hojo, K., Yamanishi, H., Karpf, A.R., Wallace, D.C. et al. (2011) Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet., 43, 595-600.
12. Verhoeven, K., De Jonghe, P., Coen, K., Verpoorten, N., Auer-Grumbach, M., Kwon, J.M., FitzPatrick, D., Schmedding, E., De Vriendt, E., Jacobs, A. et al. (2003) Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am. J. Hum. Genet., 72, 722-727.
13. Kornak, U., Mademan, I., Schinke, M., Voigt, M., Krawitz, P., Hecht, J., Barvencik, F., Schinke, T., Giesselmann, S., Beil, F.T. et al. (2014) Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3 Brain, 137, 683-692.
14. Hanada, K. (2003) Serine palmitoyltransferase, a key enzyme of sphingolipidmetabolism. Biochim. Biophys. Acta, 1632, 16-30.
15. Hornemann, T., Wei, Y. and Eckardstein, A.V.O.N. (2007) Is the mammalian serine palmitoyltransferase a high-molecularmass complex? Biochem J., 405, 157-164.
16. Nicholson, G.A., Dawkins, J.L., Blair, I.P., Kennerson, M.L., Gordon, M.J., Cherryson, A.K., Nash, J. and Bananis, T. (1996) The gene for hereditary sensory neuropathy type I (HSN-I) maps to chromosome 9q22.1-q22.3. Nat. Genet., 13, 101-104.
17. Auer-Grumbach, M., Bode, H., Pieber, T.R., Schabhüttl, M., Fischer, D., Seidl, R., Graf, E., Wieland, T., Schuh, R., Vacariu, G. et al. (2013) Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype. Eur. J. Med. Genet., 56, 266-269.
18. Rautenstrauss, B., Neitzel, B., Muench, C., Haas, J. and Holinski-Feder, E. pp. 290 of 381-290 of 381.
19. Rotthier, A., Baets, J., De Vriendt, E., Jacobs, A., Auer-Grumbach, M., Lévy, N., Bonello-Palot, N., Kilic, S.S., Weis, J., Nascimento, A. et al. (2009) Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation. Brain: J. Neurol., 132, 2699-2711.
20. Ernst, D., Murphy, S.M., Sathiyanadan, K., Wei, Y., Othman, A., Laura, M., Liu, Y.T., Penno, A., Blake, J., Donaghy, M. et al. (2015) Novel HSAN1 mutation in serine palmitoyltransferase resides at a putative phosphorylation site that is involved in regulating substrate specificity. Neuromol. Med., 17, 47-57.
21. Hornemann, T., Penno, A., Richard, S., Nicholson, G., van Dijk, F.S., Rotthier, A., Timmerman, V. and von Eckardstein, A. (2009) A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated. Neurogenetics, 10, 135-143.
22. Verhoeven, K., Coen, K., De Vriendt, E., Jacobs, A., Van Gerwen, V., Smouts, I., Pou-Serradell, A., Martin, J.J., Timmerman, V. and De Jonghe, P. (2004) SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology, 62, 1001-1002.
23. Sjöblom, T., Jones, S., Wood, L.D., Parsons, D.W., Lin, J., Barber, T.D., Mandelker, D., Leary, R.J., Ptak, J., Silliman, N. et al. (2006) The consensus coding sequences of human breast and colorectal cancers. Science, 314, 268-274.
24. Hanada, K. (1998) Mammalian cell mutants resistant to a sphingomyelin-directed cytolysin. Genetic and biochemical evidence for complex formation of the LCB1 protein with the LCB2 protein for serine palmitoyltransferase. J. Biol. Chem., 273, 33787-33794.
25. Momin, A.A., Park, H., Allegood, J.C., Leipelt, M., Kelly, S.L., Merrill, A.H. and Hanada, K. (2009) Characterization of mutant serine palmitoyltransferase 1 in LY-B cells. Lipids, 44, 725-732.
26. Meggouh, F., Bienfait, H.M.E., Weterman, M.A.J., de Visser, M. and Baas, F. (2006) Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene. Neurology, 67, 1476-1478.
27. Penno, A., Reilly, M.M., Houlden, H., Laurá, M., Rentsch, K., Niederkofler, V., Stoeckli, E.T., Nicholson, G., Eichler, F., Brown, R.H. et al. (2010) Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J. Biol. Chem., 285, 11178-11187.
28. Eichler, F.S., Hornemann, T., McCampbell, A., Kuljis, D., Penno, A., Vardeh, D., Tamrazian, E., Garofalo, K., Lee, H.-J., Kini, L. et al. (2009) Overexpression of the wild-type SPT1 subunit lowers desoxysphingolipid levels and rescues the phenotype of HSAN1. J. Neurosci.29, 14646-14651.
29. Zitomer, N.C., Mitchell, T., Voss, K.A., Bondy, G.S., Pruett, S.T., Garnier-Amblard, E.C., Liebeskind, L.S., Park, H., Wang, E., Sullards, M.C. et al. (2009) Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. J. Biol. Chem., 284, 4786-4795.
30. Cuadros, R., Montejo de Garcini, E., Wandosell, F., Faircloth, G., Fernández-Sousa, J.M. and Avila, J. (2000) The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Lett., 152, 23-29.
31. Salcedo, M., Cuevas, C., Alonso, J.L. and Otero, G. (2007) The marine sphingolipid-derived compound ES 285 triggers an atypical cell death pathway. Apoptosis, 395-409.
32. Sánchez, A.M., Malagarie-Cazenave, S., Olea, N., Vara, D., Cuevas, C. and Díaz-Laviada, I. (2008) Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo synthesis of ceramide and PKCzeta activation. Eur. J. Pharmacol., 584, 237-245.
33. Baird, R.D., Kitzen, J., Clarke, P.A., Planting, A., Reade, S., Reid, A., Welsh, L., López Lázaro, L., de las Heras, B., Judson, I.R. et al. (2009) Phase I safety, pharmacokinetic, and pharmacogenomic trial of ES-285, a novel marine cytotoxic agent, administered to adult patients with advanced solid tumors. Mol. Cancer Ther., 8, 1430-1437.
34. Schöffski, P., Dumez, H., Ruijter, R., Miguel-Lillo, B., Soto-Matos, A., Alfaro, V. and Giaccone, G. (2011) Spisulosine (ES-285) given as a weekly three-hour intravenous infusion: results of a phase I dose-escalating study in patients with advanced solid malignancies. Cancer Chemother. Pharmacol., 68, 1397-1403.
35. Vilar, E., Grünwald, V., Schöffski, P., Singer, H., Salazar, R., Iglesias, J.L., Casado, E., Cullell-young, M., Baselga, J. and Tabernero, J. (2012) A phase I dose-escalating study of ES-285, a marine sphingolipid-derived compound, with repeat dose administration in patients with advanced solid tumors. Invest. New Drugs, 30, 299-305.
36. Zuellig, R.A., Hornemann, T., Othman, A., Hehl, A.B., Bode, H., Güntert, T., Ogunshola, O.O., Saponara, E., Grabliauskaite, K., Jang, J.-H. et al. (2013) Deoxysphingolipids, a novel biomarker for type 2 diabetes, are cytotoxic for insulin-producing cells. Diabetes, 1-45.
37. Huehne, K., Zweier, C., Raab, K., Odent, S., Bonnaure-Mallet, M., Sixou, J.-L., Landrieu, P., Goizet, C., Sarlangue, J., Baumann, M. et al. (2008) Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis. Neuromusc. Disord., 18, 159-166.
38. Suh, B.C., Hong, Y.B., Nakhro, K., Nam, S.H., Chung, K.W. and Choi, B.-O. (2014) Early-onset severe hereditary sensory and autonomic neuropathy type 1 with S331F SPTLC1 mutation. Mol. Med. Rep., 9, 481-486.
39. Bejaoui, K., Uchida, Y., Yasuda, S., Ho, M., Nishijima, M., Brown, R.H., Holleran, W.M. and Hanada, K. (2002) Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis. J. Clin. Invest., 110, 1301-1308.
40. Gable, K., Han, G., Monaghan, E., Bacikova, D., Natarajan, M., Williams, R. and Dunn, T.M. (2002) Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J. Biol. Chem., 277, 10194-10200.
41. McCampbell, A., Truong, D., Broom, D.C., Allchorne, A., Gable, K., Cutler, R.G., Mattson, M.P., Woolf, C.J., Frosch, M.P., Harmon, J.M. et al. (2005) Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy. Hum. Mol. Genet., 14, 3507-3521.
42. Riley, R.T., Wang, E., Schroeder, J.J., Smith, E.R., Plattner, R.D., Abbas, H., Yoo, H.S. andMerrill, A.H. (1996) Evidence for disruption of sphingolipid metabolism as a contributing factor in the toxicity and carcinogenicity of fumonisins. Nat. Toxins, 4, 3-15.
43. Garofalo, K., Penno, A. and Schmidt, B.P. (2011) Oral l-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J. Clin. Invest., 14-16.
44. Murphy, S.M., Ernst, D., Wei, Y., Laurà, M., Liu, Y.-T., Polke, J., Blake, J., Winer, J., Houlden, H., Hornemann, T. et al. (2013) Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2. Neurology, 80, 2106-2111.
45. Rotthier, A., Penno, A., Rautenstrauss, B., Auer-Grumbach, M., Stettner, G.M., Asselbergh, B., Van Hoof, K., Sticht, H., Lévy, N., Timmerman, V. et al. (2011) Characterization of two mutations in the SPTLC1 subunit of serine palmitoyltransferase associated with hereditary sensory and autonomic neuropathy type I. Hum. Mutat., 32, E2211-E2225.
46. Dedov, V.N., Dedova, I.V., Merrill, A.H. and Nicholson, G.A. (2004)Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells. Biochim. Biophys. Acta, 1688, 168-175.
47. Gupta, S.D., Gable, K., Alexaki, A., Chandris, P., Proia, R.L., Dunn, T.M. andHarmon, J.M. (2015) Expressionof theORMDLS, modulators of serine palmitoyltransferase, is regulated by sphingolipids in mammalian cells. J. Biol. Chem., 290, 90-98.
48. Breslow, D.K., Collins, S.R., Bodenmiller, B., Aebersold, R., Simons, K., Shevchenko, A., Ejsing, C.S. and Weissman, J.S. (2010) Orm family proteins mediate sphingolipid homeostasis. Nature, 463, 1048-1053.
49. Roelants, F.M., Breslow, D.K., Muir, A., Weissman, J.S. and Thorner, J. (2011) Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA, 108, 19222-19227.
50. Hjelmqvist, L., Tuson, M., Marfany, G., Herrero, E., Balcells, S. and Gonzàlez-Duarte, R. (2002) ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins. Genome Biol., 3, RESEARCH0027-RESEARCH0027.
51. Siow, D.L. and Wattenberg, B.W. (2012) Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. J. Biol. Chem., 287, 40198-40204.
52. Han, G., Gupta, S.D., Gable, K., Niranjanakumari, S., Moitra, P., Eichler, F., Brown, R.H., Harmon, J.M. and Dunn, T.M. (2009) Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities. Proc. Natl Acad. Sci. USA, 106, 8186-8191.
53. Monaghan, E., Gable, K. and Dunn, T. (2002) Mutations in the Lcb2p subunit of serine palmitoyltransferase eliminate the requirement for the TSC3 gene in Saccharomyces cerevisiae. Yeast, 19, 659-670.
54. Harmon, J.M., Bacikova, D., Gable, K., Gupta, S.D., Han, G., Sengupta, N., Somashekarappa, N. and Dunn, T.M. (2013) Topological and functional characterization of the ssSPTs, small activating subunits of serine palmitoyltransferase. J. Biol. Chem., 288, 10144-10153.
55. Zhao, L.H., Spassieva, S., Gable, K., Gupta, S.D., Shi, L.Y., Wang, J.P., Bielawski, J., Hicks, W.L., Krebs, M.P., Naggert, J. et al. (2015) Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration. Proc. Natl Acad. Sci. USA, 112, 12962-12967.
56. Laurá, M., Murphy, S.M., Hornemann, T., Bode, H., Polke, J., Blake, J., Houlden, H. and Reilly, M.M. (2012) P42 hereditary sensory neuropathy type 1: correlation of severity and plasma atypical deoxy-sphyngoid bases. Neuromusc. Disord., 22, S18-S18.
57. Ernst, D. (2013) Regulation of deoxy-sphingolipids and their role in disease. PhD Thesis.
58. Hornemann, T., Richard, S., Rütti, M.F., Wei, Y., von Eckardstein, A., Serine-palmitoyltransferase, M., Ru, M.F. and Eckardstein, A.V. (2006) Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase. J. Biol. Chem., 281, 37275-37281.
59. Arnold, K., Bordoli, L., Kopp, J. and Schwede, T. (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics, 22, 195-201.
60. Biasini, M., Bienert, S., Waterhouse, A., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Cassarino, T.G., Bertoni, M., Bordoli, L. et al. (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res., 42, W252-W258.
61. Guex, N., Peitsch, M.C. and Schwede, T. (2009) Automated comparative protein structure modeling with SWISSMODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis, 30(Suppl. 1), S162-S173.
62. Kiefer, F., Arnold, K., Kunzli, M., Bordoli, L. and Schwede, T. (2009) The SWISS-MODEL Repository and associated resources. Nucleic Acids Res., 37, D387-D392.
63. Bi, H., Gao, Y., Yao, S., Dong, M., Headley, A.P. and Yuan, Y. (2007) Hereditary sensory and autonomic neuropathy type I in a Chinese family: British C133W mutation exists in the Chinese. Neuropathology, 27, 429-433.
64. Klein, C.J., Wu, Y., Kruckeberg, K.E., Hebbring, S.J., Anderson, S.A., Cunningham, J.M., Dyck, P.J., Klein, D.M., Thibodeau, S.N. and Dyck, P.J. (2005) SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies. J Neurol Neurosurg Psychiatry, 76, 1022-1024.
65. Geraldes, R., de Carvalho, M., Santos-Bento, M. and Nicholson, G. (2004) Hereditary sensory neuropathy type 1 in a Portuguese family-electrodiagnostic and autonomic nervous system studies. J Neurol Sci., 227, 35-38.
66. Rautenstrauss, B., Neitzel, B., Muench, C., Haas, J., Holinski-Feder, E. and Abicht, A. (2009) Late onset hereditary sensory neuropathy type 1 (hsn1) caused by a novel p.c133r missense mutation in sptlc1. Journal of Peripheral Nervous System, 14, 124-125.