Molecular mechanisms and regulation of ceramide transport

Ryan J. Perry, Neale D. Ridgway

Research output: Contribution to journalReview articlepeer-review

90 Citations (Scopus)

Abstract

De novo biosynthesis of sphingolipids begins in the endoplasmic reticulum (ER) and continues in the Golgi apparatus and plasma membrane. A crucial step in sphingolipid biosynthesis is the transport of ceramide by vesicular and non-vesicular mechanisms from its site of synthesis in the ER to the Golgi apparatus. The recent discovery of the ceramide transport protein CERT has revealed a novel pathway for the delivery of ceramide to the Golgi apparatus for sphingomyelin (SM) synthesis. In addition to a ceramide-binding START domain, CERT has FFAT (referring to two phenylalanines [FF] in an acidic tract) and pleckstrin homology (PH) domains that recognize the ER integral membrane protein VAMP-associated protein (VAP) and Golgi-associated PtdIns 4-phosphate, respectively. Mechanisms for vectorial transport involving dual-organellar targeting and sites of deposition of ceramide in the Golgi apparatus are proposed. Similar Golgi-ER targeting motifs are also present in the oxysterol-binding protein (OSBP), which regulates ceramide transport and SM synthesis in an oxysterol-dependent manner. Consequently, this emerges as a potential mechanism for integration of sphingolipid and cholesterol metabolism. The identification of organellar targeting motifs in other related lipid-binding/transport proteins indicate that concepts learned from the study of ceramide transport can be applied to other lipid transport processes.

Original languageEnglish
Pages (from-to)220-234
Number of pages15
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1734
Issue number3
DOIs
Publication statusPublished - Jun 1 2005

Bibliographical note

Funding Information:
We thank Monique Guilderson for the design and production of Fig. 2 . Work described herein was supported by operating grants from the Canadian Institutes for Health Research (CIHR) and Heart and Stroke Foundation of New Brunswick (to NDR). RJP received a doctoral award from the Heart and Stroke Foundation of Canada (HSFC).

ASJC Scopus Subject Areas

  • Molecular Biology
  • Cell Biology

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