Molecular physiology and pathophysiology of lysosomal membrane transporters

J Inherit Metab Dis. 2008 Apr;31(2):258-66. doi: 10.1007/s10545-008-0879-9. Epub 2008 Apr 15.


In contrast to lysosomal hydrolytic enzymes, the lysosomal membrane remains poorly characterized. In particular, although the genetic study of cystinosis and sialic acid storage disorders led to the identification of two lysosomal transporters for cystine and sialic acids, respectively, ten years ago, most transporters responsible for exporting lysosomal hydrolysis products to the cytosol are still unknown at the molecular level. However, two lines of investigation recently started to fill this gap in the knowledge of lysosomal biology. First, novel proteomic approaches are now able to provide a reliable inventory of lysosomal membrane proteins. On the other hand, a novel functional approach based on intracellular trafficking mechanisms allows direct transport measurement in whole cells by redirecting recombinant lysosomal transporters to the cell surface. After surveying the current state of knowledge in this field, the review focuses on the sialic acid transporter sialin and shows how recent functional data using the above whole-cell approach shed new light on the pathogenesis of sialic acid storage disorders by revealing the existence of a residual transport activity associated with Salla disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Predisposition to Disease
  • Humans
  • Lysosomes / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism*
  • Metabolism, Inborn Errors / physiopathology
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Phenotype
  • Protein Transport
  • Proteomics / methods
  • Sialic Acid Storage Disease / genetics
  • Sialic Acid Storage Disease / metabolism
  • Symporters / genetics
  • Symporters / metabolism


  • Membrane Transport Proteins
  • Organic Anion Transporters
  • Symporters
  • sialic acid transport proteins