Abstract
Lysosomes are intracellular organelles acidified by a vacuolar proton pump. They contain a wide variety of acid hydrolases for degradation of intra- and extracellular macromolecules and are surrounded by a single lipid bilayer membrane. Initially the lysosomal membrane was considered to be only a mechanical border separating the acid lysosomal environment from the neutral environment of the surrounding cytoplasm. Therefore lysosomes were considered the “terminal degradative compartment” of the cell and their function was strictly linked to cellular catabolism. However, two inborn errors of metabolism — cystinosis and sialicacid storage disorders — have contributed to a more thorough understanding of lysosomal membrane transport function.As we know now, the lysosomal membrane contains special transport proteins for both export and import (Mancini et al. 2000).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aula, P., Autio, S., Raivio, K.O., Rapola, J., Thodén, C.J., Koskela, S.L., et al. (1979). “Salla disease.” A New Lysosomal Storage Disorder. Arch. Neurol., 36, 88–94.
Aula, P., Renlund, M., and Raivio, K. ( 1986). Screening of Inherited Oligosaecharidurias among Mentally Retarded Patients in Northern Finland. J. Ment. Defic. Res., 30, 365–368.
Aula, N., Salomaki, P., Timonen, R., Verheijen, E, Mancini, G., Mansson, J.E., et al. (2000). The Spectrum of SLCI 7A5-Gene Mutations Resulting in Free Sialic Acid-Storage Diseases Indicates Some GenotypePhenotype Correlation. Am. J. Hum. Genet., 67, 832–840.
Bellocchio, E.E., Reimer, R.J., Fremeau, R.T., Jr, and Edwards, R.H. (2000). Uptake of Glutamate into Synaptic Vesicles by an Inorganic Phosphate Transporter. Science, 289, 957–960.
Haataja, L., Parkkola, R., Sonninen, P., Vanhanen, S.L., Schleutker, L, Aarimaa, T., et al. (1994 ). Phenotypic Variation and Magnetic Resonance Imaging (MRI) in Salla Disease, a Free Sialic Acid Storage Disorder. Neuropediatrics, 25, 238–244.
Havelaar, A.C., Mancini, G.M.S., Beerens, C.E.M.T., Souren, R.M.A., and Verheijen, EW. ( 1998). Purification of the Lysosomal Sialic Acid Transporter. Functional Characteristics of a Monocarboxylate Transporter. J. Biol. Chem., 273, 34568–34574.
Havelaar, A.C., Beercns, C.E., Mancini, G.M.S., and Verheijen, EW. (1999). Transport of Organic Anions by the Lysosomal Sialic Acid Transporter: A Functional Approach toward s the Gene for Sialic Acid Storage Disease. FEBS Lett., 446, 65–68.
Hayashi, M., Otsuka, M., Morimoto, R., Hirota, S., Yatsushiro, S., Takeda, J., et al. (2001). Differentiation-Associated Na+-Dependent Inorganic Phosphate Cotransporter (DNPI) is a Vesicular Glutamate Transporter in Endocrine Glutamatergic Systems. J. Biol. Chem., 276, 43400–43406.
Leppänen. P., Isosornppi, L, Schleutker, J., Aula, P., and Peltonen, L. (1996). A Physical Map of the 6q 14-q 15 Region Harboring the Locus for the Lysosomal Membrane Sialic Acid Transport Defect. Genomics, 37, 62–67.
Mancini, G.M.S., de Jonge, H.R., Galjaard, H., and Verheijen, EW. (1989). Characterization of a ProtonDriven Carrier for Sialic Acid in the Lysosomal Membrane. Evidence for a Group-Specific Transport System for Acidic Monosaccharides. J. Biol. Chem., 264,15247–15254.
Mancini, G.M.S., Beerens, C.E.M.T., Aula, P.P., and Verheijen, EW. (1991). SialicAcid Storage Diseases. A Multiple Lysosomal Transport Defect for Acidic Monosaccharides. J. clin. Invest., 87, 1329–1335.
Mancini, G.M.S., Beerens, C.E.M.T., Galjaard. H., and Verheijen, EW. (1992a). Functional Reconstitution of the Lysosomal Sialic Acid Carrier into Proteoliposornes. Proc. Natl Acad. Sci. USA, 89, 6609–6613.
Mancini, G.M.S., Hu, P., Verheijen, EW., van Diggelen, O.P., Janse, H.C., Kleijer, W.J., et al. ( 1992b). Salla Disease Variant in a Dutch Patient. Potential Value of Polymorphonuclear Leucocytes for Heterozygote Detection. Eur. J. Pediatr., 151, 590–595.
Mancini, G.M.S., Havelaar, A.C., and Verheijen, EW (2000). Lysosomal Transport Disorders. J. Inherit. Metab. Dis., 23, 278–292.
Pao, S.S., Paulsen, LT., and Saier, M.H., Jr (1998). Major Facilitator Superfamily. Microbial. Mol. Biol. Rev., 62, 1–34.
Pitto, M., Chigomo, Y, Renlund, M., and Tettamanti, G. (1996). Impairment of Gangliosid e Metabolism in Cultured Fibroblasts from Salla Patients. Clin. Chim. Acta, 247, 143–157.
Renlund, M., Tietze, E, and Gahl, W.A. ( 1986). Defective Sialic Acid Egress from Isolated Fibroblast Lysosomes of Patients with Salla Disease. Science, 232, 759–762.
Salomaki, P., Aula, N., Juvonen, Y, Renlund, M., and Aula, P. (2001). Prenatal Detection of Free Sialic Acid Storage Disease: Genetic and Biochemical Studies in Nine Families. Prenat. Diagn., 21,354–358.
Schauer, R. (2000). Achievements and Challenges of Sialic Acid Research. Glycoconj. J., 17,485–499.
Schleutker, J., Laine, A.P., Haataja, L., Renlund, M., Weissenbach, J., Aula, P., et al. (1995a). Link age Disequilibrium Utilized to Establish a Refined Genetic Position of the Salla Disease Locus on 6q14-q15. Genomics, 27, 286–292.
Schleutker, J., Leppanen, P., Mansson, J.-E., Erikson, A., Weissenbach, J., Peltonen, L., et al. (1995b). Lysosomal Free Sialic Acid Storage Disorders with Different Phenotypic Presentations, ISSD and Salla disease, Represent Allelic Disorder s on 6q14-15. Am. J. Hum. Genet., 57, 893–901.
Schwarzkopf, M., Knobeloch, K.P., Rohde, E., Hinderlich, S., Wiechens, N., Lucka, L., et al. (2002). Sialylation is Essential for Early Development in Mice. Proc. Natl Acad. Sci. USA, 99, 5267–5270.
Verheijen, EW, Verbeck, E., Aula, N., Beerens, C.E., Havelaar, A.C., Joosse, M., et al. (1999). A New Gene, Encoding an Anion Transporter, is Mutated in Sialic Acid Storage Diseases. Nat. Genet., 23, 462–465.
Weiss, P., Tietze, E, Gahl, WA., Seppala, R., and Ashwell, G. (1989). Identification of the Metabolic Defect in Sialuria. J. Biol. Chem., 264, 17635–17636.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Verheijen, F.W., Mancini, G.M.S. (2003). Lysosomal sialic acid transporter sialin (SLC17A5): sialic acid storage disease (SASD). In: Bröer, S., Wagner, C.A. (eds) Membrane Transporter Diseases. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9023-5_15
Download citation
DOI: https://doi.org/10.1007/978-1-4419-9023-5_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4761-3
Online ISBN: 978-1-4419-9023-5
eBook Packages: Springer Book Archive