Regulated cleavage of intracellular glycosylphosphatidylinositol in a trypanosome. Peroxisome-to-endoplasmic reticulum translocation of a phospholipase C.

Abstract

Cell exposure to hypo-osmolarity and alkalinity triggers a spectrum of responses including activation of phospholipases. Glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC) is expressed in Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. We examined possible contributions of GPI-PLC to the response of T. brucei to hypo-osmotic or mildly alkaline conditions. GPIs were detected at the endoplasmic reticulum (ER). They were cleaved after exposure of T. brucei to hypo-osmolarity or mild alkalinity, which also, strikingly, caused translocation of GPI-PLC from glycosomes (peroxisomes) to the ER. A catalytically inactive Gln81Leu mutant of GPI-PLC failed to cleave GPIs despite being transported from glycosomes to the ER after hypo-osmotic or mild alkaline treatment of the parasites. In contrast, a Cys347Ser mutant of the enzyme could not exit glycosomes after treatment of cells expressing the protein with mild base or hypo-osmotic buffer. We conclude that: (a) GPI-PLC contributes to loss of GPIs in T. brucei treated with hypo-osmotic or mildly alkaline buffer; (b) access of GPI-PLC to its substrate in vivo can be regulated post-translationally; (c) translocation of GPI-PLC from glycosomes to the ER is important for in vivo cleavage of GPIs; (d) Cys347 is part of a peptide motif required for post-translational targeting of GPI-PLC to the ER. Glycosome-to-ER movement of GPI-PLC reveals a novel pathway for intracellular protein traffic. The physiological significance of GPI digestion in cells exposed to mildly alkalinity or hypo-osmolarity is discussed.

• Authors: Sandesh Subramanya, Kojo Mensa-Wilmot
• Journal: The FEBS journal (FEBS J) Vol. 273 Issue 10 Pg. 2110-26 (May 2006) ISSN: 1742-464X [Print] England
• PMID: 16649989 (Publication Type: Journal Article)

Chemical References

• Glycosylphosphatidylinositols
• Type C Phospholipases

Topics

• Animals
• Endoplasmic Reticulum (chemistry, metabolism)
• Glycosylphosphatidylinositols (genetics, metabolism)
• Hydrogen-Ion Concentration
• Mutation
• Osmosis
• Peroxisomes (chemistry, metabolism)
• Protein Transport
• Trypanosoma brucei brucei (chemistry, metabolism)
• Type C Phospholipases (genetics, metabolism)