Regulation of ganglioside biosynthesis in the nervous system

Robert K. Yu, Erhard Bieberich, Tian Xia, Guichao Zeng

Research output: Contribution to journalReview article

128 Scopus citations

Abstract

Ganglioside biosynthesis is strictly regulated by the activities of glycosyltransferases and is necessarily controlled at the levels of gene transcription and posttranslational modification. Cells can switch between expressing simple and complex gangliosides or between different series within these two groups during brain development. The sequential biosynthesis of gangliosides in parallel enzymatic pathways, however, requires fine-tuned subcellular sequestration and orchestration of glycosyltransferases. A popular model predicts that this regulation is achieved by the vectorial organization of ganglioside biosynthesis: sequential biosynthetic steps occur with the traffic of ganglioside intermediates through subsequent subcellular compartments. Here, we review current models for the subcellular distribution of glycosyltransferases and discuss results that suggest a critical role of N-glycosylation for the processing, transport, and complex formation of these enzymes. In this context, we attempt to illustrate the regulation of ganglioside biosynthesis as well as the biological significance of N-glycosylation as a posttranslational regulatory mechanism. We also review the results of analyses of the 5′ regulatory sequences of several glycosyltransferases in ganglioside biosynthesis and provide insights into how their synthesis can be regulated at the level of transcription.

Original languageEnglish (US)
Pages (from-to)783-793
Number of pages11
JournalJournal of Lipid Research
Volume45
Issue number5
DOIs
StatePublished - May 2004

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Keywords

  • Ceramide
  • Endoplasmic reticulum
  • Glycosyltransferase
  • Golgi
  • N-glycosylation
  • Posttranslational modification
  • Transcription
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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