The Role of Saposins in Auditory and Vestibular Systems
Main Article Content
Abstract
Abstract
Prosaposin, and its cleaved byproducts saposin A-D, are crucial proteins necessary for glycoshpingolipid degradation and metabolism. Mutations in these proteins can lead to devastating lysosomal storage diseases, including Gaucher’s disease, symptoms of which often include hearing loss. Until recently, little was known about the role that prosaposin and saposins A-D played in auditory and vestibular system function. Early studies in knockout mouse models showed prosaposin to be important for normal cochlear innervation and maintenance of normal hearing (Akil et al., 2006). Severe vestibular dysfunction paired with inclusion body accumulation in the vestibular end-organs of prosaposin KO mice suggests its role in the maintenance of normal hearing and the maturation of normal vestibular system function (Akil et al., 2012). To determine if these phenotypes were attributable to the loss of prosaposin as a whole or one of its constituent proteins, saposin A-D, KO mice of individual saposins were subsequently studied. Given the nature of the hearing loss, as well as efferent and afferent neuronal sprouting in the prosaposin KO mouse, it was hypothesized that saposin C, a protein known for its neurotigenic properties, was responsible for these changes. However, a null-mutant mouse lacking both saposin C and D showed no effect on hearing (Lustig et al., 2015). In contrast, a loss of functional saposin B led to a progressive sulfatide accumulation in satellite cells around cochlear spiral ganglion (SG) neurons resulting in satellite cell degeneration, SG degeneration, and ultimately, loss of hearing (Akil et al., 2015). While saposin B KO mice did not show any vestibular dysfunction phenotype, vestibular evoked potentials demonstrated profound vestibular dysfunction likely attributable to the large-scale neuronal degeneration (Akil et al., 2015). Furthermore, the data suggests that saposin B appears to have a much greater role in auditory neuronal maintenance and balance than saposin C and/or D.
Article Details
How to Cite
AKIL, Omar; ROUSE, Stephanie; LUSTIG, Lawrence.
The Role of Saposins in Auditory and Vestibular Systems.
Medical Research Archives, [S.l.], v. 2, n. 2, aug. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/312>. Date accessed: 22 dec. 2024.
Keywords
Key Words: prosaposin, saposin A, B, C, D, glycosphingolipid hydrolases, cochlea, hearing, balance, vestibular, auditory
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
References
Akil O, Chang J, Hiel H et al. Progressive deafness and altered cochlear innervation in knock-out mice lacking prosaposin. J Neuroscience 2006; 26: 13076-13088.
Akil O, Lustig LR. Severe vestibular dysfunction and altered vestibular innervation in mice lacking prosaposin. Neuroscience research 2012; 72: 296-305.
Akil O, Sun Y, Zhang W, Ku T, Lee C, Jones S, Grabowski G, Lustig LR. Spiral Ganglion Degeneration and Hearing Loss as a Consequence of Satellite Cell Death in Saposin B-Deficient Mice. J Neuroscience 2015; 35(7): 3263-3275.
Azuma N, O'Brien JS, Moser HW, Kishimoto Y. Stimulation of acid ceramidase activity by saposin D. Archives of biochemistry and biophysics 1994; 311: 354-357.
Bamiou DE, Campbell P, Liasis A et al. Audometric abnormalities in children with Gaucher disease type 3. Neuropediatrics 2001; 32: 136-141.
Campbell PE, Harris CM, Vellodi A. Deterioration of the auditory brainstem response in children with type 3 Gaucher disease. Neurology 2004; 63: 385-387.
Ciaffoni F, Tatti M, Boe Aet al. Saposin B binds and transfers phospholipids. J Lipid Res. 2006; 47: 1045-1053
Coenen R, Gieselmann V, Lullmann-Rauch R. Morphological alterations in the inner ear of the arylsulfatase A-deficient mouse. Acta neuropathologica 2001; 101: 491-498.
Colombaioni L, Garcia-Gil M. Sphngolipid metabolites in neural signalling and function. Brain Res. Rev. 2004; 46(3): 328-355.
D'Hooge R, Coenen R, Gieselmann V, Lullmann-Rauch R, De Deyn PP. Decline in brainstem auditory-evoked potentials coincides with loss of spiral ganglion cells in arylsulfatase A-deficient mice. Brain Res. 1999; 847: 352-356.
Deconinck N, Messaaoui A, Ziereisen Fet al. Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency. Eur. J. Paediatr. Neurol. 2008; 12: 46-50.
de Hosson LD, van de Warrenburg BP, Preijers FWet al. Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature. Bone Marrow Transplant 2011; 46: 1071-1076.
Fabbro D, Grabowski GA. Human acid β-glucosidase: use of inhibitory and activating monoclonal antibodies to investigate the enzyme’s catalytic mechanism and saposin A and C binding sites. J. Biol. Chem 1991; 266: 15021-15027.
Fujita N, Suzuki K, Vanier MTet al. Targeted disruption of the mouse sphingolipid activator protein gene: a complex phenotype, including severe leukodystrophy and wide-spread storage of multiple sphingolipids. Human molecular genetics 1996; 5: 711-725.
Furst W, Sandhoff K. Activator proteins and topology of lysosomal sphingolipid catabolism. Biochimica et biophysica acta 1992; 1126: 1-16.
Gao J, Yin D, Yao Y, Williams TD, Squier TC. Progressive decline in the
ability of calmodulin isolated from aged brain to activate the plasma mem-
brane Ca-ATPase. Biochemistry 1998; 37: 9536–9548
Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics 2010; 41: 1-6.
Hakomori S. Chemistry of glycosphingolipids. Handbook of lipid research 1983; 3: 1-164.
Henseler M., Klein A., Glombitza G.J., Suzuki K., Sandhoff K. Expression of the three alternative forms of the sphingolipid activator protein precursor in baby hamster kidney cells and functional assays in a cell culture system. J. Biol. Chem. 1996; 271: 8416–8423
Hess B, Saftig P, Hartmann Det al. Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy. Proceedings of the National Academy of Sciences of the United States of America 1996; 93: 14821-14826.
Hineno, T., A. Sano, K. Kondoh, S. Ueno, Y. Kakimoto, and K. Yoshida. Secretion of sphingolipid hydrolase activator precursor, prosaposin. Biochem. Biophys. Res.
Commun. 1991; 176: 668-674.
Hiraiwa M, Soeda S, Kishimoto Y, O'Brien JS. Binding and transport of gangliosides by prosaposin. Proceedings of the National Academy of Sciences of the United States of America 1992; 89: 11254-11258.
Holtschmidt H, Sandhoff K, Kwon HY, Harzer K, Nakano T, Suzuki K. Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease. The Journal of biological chemistry 1991; 266: 7556-7560.
Inui K, Kao FT, Fujibayashi Set al. The gene coding for a sphingolipid activator protein, SAP-1, is on human chromosome 10. Human genetics 1985; 69: 197-200.
Jatzkewitz H. Eine neue Methode zur quantitativen Ultramikrobestimmung der Sphingolipoide aus Gehirm. Hoppe-Seyler’s Z. Physiol. Chem. 1964; 336: 25-39.
Kishimoto Y., Hiraiwa M., O’Brien J.S. Saposins: structure, function, distribution, and molecular genetics. J. Lipid Res. 1992; 33: 1255–1267
Kotani Y, Matsuda S, Sakanaka M, Kondoh K, Ueno S, Sano A. Prosaposin facilitates sciatic nerve regeneration in vivo. J Neurochem. 1996; 66: 2019-2025.
Kujawa SG, Liberman MC. Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss. J Neurosci 2009; 29: 14077-14085.
Land MF. Motion and vision: why animals move their eyes. J Comp Physiol A. 1999; 185: 341–352
Li SC, Sonnino S, Tettamanti G, Li YT. Characterization of a nonspecific activator protein for the enzymatic hydrolysis of glycolipids. The Journal of biological chemistry 1988; 263: 6588-6591.
Lin HW, Furman AC, Kujawa SG, Liberman MC. Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift. J Assoc. Res. Otolaryngol. 2011; 12: 605-616.
Lustig LR, Alemi S, Sun Y, Grabowski G, Akil O. Role of Saposin C and D in auditory and vestibular function. Laryngoscope. 2015 Jul 21. doi: 10.1002/lary.25479.
Marzella PL, Clark GM. Growth factors, auditory neurones and cochlear implants: a review. Acta Otolaryngol. 1999; 119: 407–412.
Matsuda J, Kido M, Tadano-Aritomi Ket al. Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse. Human molecular genetics 2004; 13: 2709-2723.
Morimoto S, Martin BM, Kishimoto Y, O'Brien JS. Saposin D: a sphingomyelinase activator. Biochemical and biophysical research communications 1988; 156: 403-410.
Morimoto S, Martin BM, Yamamoto Y, Kretz KA, O'Brien JS, Kishimoto Y. Saposin A: second cerebrosidase activator protein. Proceedings of the National Academy of Sciences of the United States of America 1989; 86: 3389-3393.
Nakaizumi T, Kawamoto K, Minoda R, Raphael Y. Adenovirusmediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage. Audiol. Neurootol. 2004; 9: 135–143.
O'Brien JS, Kretz KA, Dewji N, Wenger DA, Esch F, Fluharty AL. Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus. Science 1988; 241: 1098-1101.
O'Brien JS, Kishimoto Y. Saposin proteins: structure, function, and role in human lysosomal storage disorders. FASEB J 1991; 5: 301-308.
O'Brien JS, Carson GS, Seo HC, Hiraiwa M, Kishimoto Y. Identification of prosaposin as a neurotrophic factor. Proceedings of the National Academy of Sciences of the United States of America 1994; 91: 9593-9596.
O'Brien JS, Carson GS, Seo HCet al. Identification of the neurotrophic factor sequence of prosaposin. Faseb. J. 1995; 9: 681-685.
Paton BC, Schmid B, Kustermann-Kuhn B, Poulos A, Harzer K. Additional biochemical findings in a patient and fetal sibling with a genetic defect in the sphingolipid activator protein (SAP) precursor, prosaposin. Evidence for a deficiency in SAP-1 and for a normal lysosomal neuraminidase. Biochem J 1992; 285 (2): 481-488.
Radin, N. S. The cohydrolases for cerebroside 0-glucosidase. In The Molecular Basis of Lysosomal Storage Disorders. R. 0. Brady and J. A. Barranger, editors. Academic Press, New York. 1984; 93-112.
Sandhoff K. The hydrolysis of Tay-Sachs ganglioside (TSG) by human N-acetyl-β-D-hexosaminidase A. FEBS Lett. 1970; 11: 342–344
Sandhoff K, van Echten G, Schroder M, Schnabel D, Suzuki K. Metabolism of glycolipids: the role of glycolipid-binding proteins in the function and pathobiochemistry of lysosomes. Biochem. Soc. Trans. 1992; 20: 695-699.
Sandhoff K, Kolter T, Van Echten-Deckert G. Sphingolipid metabolism. Sphingoid analogs, sphingolipid activator proteins, and the pathology of the cell. Annals of the New York Academy of Sciences 1998; 845: 139-151.
Sandhoff K. The GM2-gangliosidoses and the elucidation of the beta-hexosaminidase system. Adv Genet 2001; 44: 67-91.
Sandhoff K. My journey into the world of sphingolipids and sphingolipidoses. Proc Jpn Acad Ser B Phys Boil Sci. 2012; 88(10): 554-82.
Schlote W., Harzer K., Christomanou H., Paton B.C., Kustermann-Kuhn B., Schmid B., Seeger J., Beudt U., Schuster I., Langenbeck U. Sphingolipid activator protein 1 deficiency in metachromatic leucodystrophy with normal arylsulphatase A activity. A clinical, morphological, biochemical and immunological study. Eur. J. Pediatr. 1991; 150: 584–591
Shepherd RK, Hardie NA Deafness-induced changes in the auditory pathway: implications for cochlear implants. Audiol Neurootol. 2001; 6: 305–318
Spoor F, Bajpai S, Hussain ST, Kumar K, Thewissen JG. Vestibular evidence for the evolution of aquatic behaviour in early cetaceans. Nature. 2002; 417: 163–166
Sundaram SK, Fan JH, Lev M. A neutral galactocerebroside sulfate sulfatidase from mouse brain. J Biol Chem 1995; 270: 10187-10192
Sun Y, Qi X, Witte DPet al. Prosaposin: threshold rescue and analysis of the "neuritogenic" region in transgenic mice. Molecular genetics and metabolism 2002; 76: 271-286.
Sun Y, Witte DP, Jin P, Grabowski GA. Analyses of temporal regulatory elements of the prosaposin gene in transgenic mice. Biochem J 2003; 370: 557-566.
Sun Y, Witte DP, Zamzow Met al. Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and alpha-hydroxy ceramide accumulation, and altered prosaposin trafficking. Human molecular genetics 2007; 16: 957-971.
Sun Y, Witte DP, Ran Het al. Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice. Human molecular genetics 2008; 17: 2345-2356.
Terashita T, Saito S, Miyawaki Ket al. Localization of prosaposin in rat cochlea. Neuroscience research 2007; 57: 372-378
Wenger DA, DeGala G, Williams Cet al. Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency. Am J Med Genet 1989; 33: 255-265.
Walls G. The evolutionary history of eye movements. Vision Research. 1962; 2: 69–80.
Zhang XL, Rafi MA, DeGala G, Wenger DA. Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. Proceedings of the National Academy of Sciences of the United States of America 1990; 87: 1426-1430.
Akil O, Chang J, Hiel H et al. Progressive deafness and altered cochlear innervation in knock-out mice lacking prosaposin. J Neuroscience 2006; 26: 13076-13088.
Akil O, Lustig LR. Severe vestibular dysfunction and altered vestibular innervation in mice lacking prosaposin. Neuroscience research 2012; 72: 296-305.
Akil O, Sun Y, Zhang W, Ku T, Lee C, Jones S, Grabowski G, Lustig LR. Spiral Ganglion Degeneration and Hearing Loss as a Consequence of Satellite Cell Death in Saposin B-Deficient Mice. J Neuroscience 2015; 35(7): 3263-3275.
Azuma N, O'Brien JS, Moser HW, Kishimoto Y. Stimulation of acid ceramidase activity by saposin D. Archives of biochemistry and biophysics 1994; 311: 354-357.
Bamiou DE, Campbell P, Liasis A et al. Audometric abnormalities in children with Gaucher disease type 3. Neuropediatrics 2001; 32: 136-141.
Campbell PE, Harris CM, Vellodi A. Deterioration of the auditory brainstem response in children with type 3 Gaucher disease. Neurology 2004; 63: 385-387.
Ciaffoni F, Tatti M, Boe Aet al. Saposin B binds and transfers phospholipids. J Lipid Res. 2006; 47: 1045-1053
Coenen R, Gieselmann V, Lullmann-Rauch R. Morphological alterations in the inner ear of the arylsulfatase A-deficient mouse. Acta neuropathologica 2001; 101: 491-498.
Colombaioni L, Garcia-Gil M. Sphngolipid metabolites in neural signalling and function. Brain Res. Rev. 2004; 46(3): 328-355.
D'Hooge R, Coenen R, Gieselmann V, Lullmann-Rauch R, De Deyn PP. Decline in brainstem auditory-evoked potentials coincides with loss of spiral ganglion cells in arylsulfatase A-deficient mice. Brain Res. 1999; 847: 352-356.
Deconinck N, Messaaoui A, Ziereisen Fet al. Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency. Eur. J. Paediatr. Neurol. 2008; 12: 46-50.
de Hosson LD, van de Warrenburg BP, Preijers FWet al. Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature. Bone Marrow Transplant 2011; 46: 1071-1076.
Fabbro D, Grabowski GA. Human acid β-glucosidase: use of inhibitory and activating monoclonal antibodies to investigate the enzyme’s catalytic mechanism and saposin A and C binding sites. J. Biol. Chem 1991; 266: 15021-15027.
Fujita N, Suzuki K, Vanier MTet al. Targeted disruption of the mouse sphingolipid activator protein gene: a complex phenotype, including severe leukodystrophy and wide-spread storage of multiple sphingolipids. Human molecular genetics 1996; 5: 711-725.
Furst W, Sandhoff K. Activator proteins and topology of lysosomal sphingolipid catabolism. Biochimica et biophysica acta 1992; 1126: 1-16.
Gao J, Yin D, Yao Y, Williams TD, Squier TC. Progressive decline in the
ability of calmodulin isolated from aged brain to activate the plasma mem-
brane Ca-ATPase. Biochemistry 1998; 37: 9536–9548
Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics 2010; 41: 1-6.
Hakomori S. Chemistry of glycosphingolipids. Handbook of lipid research 1983; 3: 1-164.
Henseler M., Klein A., Glombitza G.J., Suzuki K., Sandhoff K. Expression of the three alternative forms of the sphingolipid activator protein precursor in baby hamster kidney cells and functional assays in a cell culture system. J. Biol. Chem. 1996; 271: 8416–8423
Hess B, Saftig P, Hartmann Det al. Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy. Proceedings of the National Academy of Sciences of the United States of America 1996; 93: 14821-14826.
Hineno, T., A. Sano, K. Kondoh, S. Ueno, Y. Kakimoto, and K. Yoshida. Secretion of sphingolipid hydrolase activator precursor, prosaposin. Biochem. Biophys. Res.
Commun. 1991; 176: 668-674.
Hiraiwa M, Soeda S, Kishimoto Y, O'Brien JS. Binding and transport of gangliosides by prosaposin. Proceedings of the National Academy of Sciences of the United States of America 1992; 89: 11254-11258.
Holtschmidt H, Sandhoff K, Kwon HY, Harzer K, Nakano T, Suzuki K. Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease. The Journal of biological chemistry 1991; 266: 7556-7560.
Inui K, Kao FT, Fujibayashi Set al. The gene coding for a sphingolipid activator protein, SAP-1, is on human chromosome 10. Human genetics 1985; 69: 197-200.
Jatzkewitz H. Eine neue Methode zur quantitativen Ultramikrobestimmung der Sphingolipoide aus Gehirm. Hoppe-Seyler’s Z. Physiol. Chem. 1964; 336: 25-39.
Kishimoto Y., Hiraiwa M., O’Brien J.S. Saposins: structure, function, distribution, and molecular genetics. J. Lipid Res. 1992; 33: 1255–1267
Kotani Y, Matsuda S, Sakanaka M, Kondoh K, Ueno S, Sano A. Prosaposin facilitates sciatic nerve regeneration in vivo. J Neurochem. 1996; 66: 2019-2025.
Kujawa SG, Liberman MC. Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss. J Neurosci 2009; 29: 14077-14085.
Land MF. Motion and vision: why animals move their eyes. J Comp Physiol A. 1999; 185: 341–352
Li SC, Sonnino S, Tettamanti G, Li YT. Characterization of a nonspecific activator protein for the enzymatic hydrolysis of glycolipids. The Journal of biological chemistry 1988; 263: 6588-6591.
Lin HW, Furman AC, Kujawa SG, Liberman MC. Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift. J Assoc. Res. Otolaryngol. 2011; 12: 605-616.
Lustig LR, Alemi S, Sun Y, Grabowski G, Akil O. Role of Saposin C and D in auditory and vestibular function. Laryngoscope. 2015 Jul 21. doi: 10.1002/lary.25479.
Marzella PL, Clark GM. Growth factors, auditory neurones and cochlear implants: a review. Acta Otolaryngol. 1999; 119: 407–412.
Matsuda J, Kido M, Tadano-Aritomi Ket al. Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse. Human molecular genetics 2004; 13: 2709-2723.
Morimoto S, Martin BM, Kishimoto Y, O'Brien JS. Saposin D: a sphingomyelinase activator. Biochemical and biophysical research communications 1988; 156: 403-410.
Morimoto S, Martin BM, Yamamoto Y, Kretz KA, O'Brien JS, Kishimoto Y. Saposin A: second cerebrosidase activator protein. Proceedings of the National Academy of Sciences of the United States of America 1989; 86: 3389-3393.
Nakaizumi T, Kawamoto K, Minoda R, Raphael Y. Adenovirusmediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage. Audiol. Neurootol. 2004; 9: 135–143.
O'Brien JS, Kretz KA, Dewji N, Wenger DA, Esch F, Fluharty AL. Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus. Science 1988; 241: 1098-1101.
O'Brien JS, Kishimoto Y. Saposin proteins: structure, function, and role in human lysosomal storage disorders. FASEB J 1991; 5: 301-308.
O'Brien JS, Carson GS, Seo HC, Hiraiwa M, Kishimoto Y. Identification of prosaposin as a neurotrophic factor. Proceedings of the National Academy of Sciences of the United States of America 1994; 91: 9593-9596.
O'Brien JS, Carson GS, Seo HCet al. Identification of the neurotrophic factor sequence of prosaposin. Faseb. J. 1995; 9: 681-685.
Paton BC, Schmid B, Kustermann-Kuhn B, Poulos A, Harzer K. Additional biochemical findings in a patient and fetal sibling with a genetic defect in the sphingolipid activator protein (SAP) precursor, prosaposin. Evidence for a deficiency in SAP-1 and for a normal lysosomal neuraminidase. Biochem J 1992; 285 (2): 481-488.
Radin, N. S. The cohydrolases for cerebroside 0-glucosidase. In The Molecular Basis of Lysosomal Storage Disorders. R. 0. Brady and J. A. Barranger, editors. Academic Press, New York. 1984; 93-112.
Sandhoff K. The hydrolysis of Tay-Sachs ganglioside (TSG) by human N-acetyl-β-D-hexosaminidase A. FEBS Lett. 1970; 11: 342–344
Sandhoff K, van Echten G, Schroder M, Schnabel D, Suzuki K. Metabolism of glycolipids: the role of glycolipid-binding proteins in the function and pathobiochemistry of lysosomes. Biochem. Soc. Trans. 1992; 20: 695-699.
Sandhoff K, Kolter T, Van Echten-Deckert G. Sphingolipid metabolism. Sphingoid analogs, sphingolipid activator proteins, and the pathology of the cell. Annals of the New York Academy of Sciences 1998; 845: 139-151.
Sandhoff K. The GM2-gangliosidoses and the elucidation of the beta-hexosaminidase system. Adv Genet 2001; 44: 67-91.
Sandhoff K. My journey into the world of sphingolipids and sphingolipidoses. Proc Jpn Acad Ser B Phys Boil Sci. 2012; 88(10): 554-82.
Schlote W., Harzer K., Christomanou H., Paton B.C., Kustermann-Kuhn B., Schmid B., Seeger J., Beudt U., Schuster I., Langenbeck U. Sphingolipid activator protein 1 deficiency in metachromatic leucodystrophy with normal arylsulphatase A activity. A clinical, morphological, biochemical and immunological study. Eur. J. Pediatr. 1991; 150: 584–591
Shepherd RK, Hardie NA Deafness-induced changes in the auditory pathway: implications for cochlear implants. Audiol Neurootol. 2001; 6: 305–318
Spoor F, Bajpai S, Hussain ST, Kumar K, Thewissen JG. Vestibular evidence for the evolution of aquatic behaviour in early cetaceans. Nature. 2002; 417: 163–166
Sundaram SK, Fan JH, Lev M. A neutral galactocerebroside sulfate sulfatidase from mouse brain. J Biol Chem 1995; 270: 10187-10192
Sun Y, Qi X, Witte DPet al. Prosaposin: threshold rescue and analysis of the "neuritogenic" region in transgenic mice. Molecular genetics and metabolism 2002; 76: 271-286.
Sun Y, Witte DP, Jin P, Grabowski GA. Analyses of temporal regulatory elements of the prosaposin gene in transgenic mice. Biochem J 2003; 370: 557-566.
Sun Y, Witte DP, Zamzow Met al. Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and alpha-hydroxy ceramide accumulation, and altered prosaposin trafficking. Human molecular genetics 2007; 16: 957-971.
Sun Y, Witte DP, Ran Het al. Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice. Human molecular genetics 2008; 17: 2345-2356.
Terashita T, Saito S, Miyawaki Ket al. Localization of prosaposin in rat cochlea. Neuroscience research 2007; 57: 372-378
Wenger DA, DeGala G, Williams Cet al. Clinical, pathological, and biochemical studies on an infantile case of sulfatide/GM1 activator protein deficiency. Am J Med Genet 1989; 33: 255-265.
Walls G. The evolutionary history of eye movements. Vision Research. 1962; 2: 69–80.
Zhang XL, Rafi MA, DeGala G, Wenger DA. Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. Proceedings of the National Academy of Sciences of the United States of America 1990; 87: 1426-1430.