Turnover of Variant Surface Glycoprotein in Trypanosoma brucei Is a Bimodal Process

Abstract

African trypanosomes, the protozoan agent of human African trypanosomaisis, avoid the host immune system by switching expression of the variant surface glycoprotein (VSG). VSG is a long-lived protein that has long been thought to be turned over by hydrolysis of its glycolipid membrane anchor.

The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids

“…However, it has not yet been demonstrated whether sialic acid capping is important for parasite survival. Cross, 1975;Cross et al, 2014;Mugnier et al, 2016 TfR BSF Transferrin uptake Steverding et al, 1994;Mussmann et al, 2003Mussmann et al, , 2004 GPI-PLC BSF Phospholipase, implicated in VSG shedding Bülow et al, 1989;Gruszynski et al, 2003;Garrison et Summary of the GPI-anchored surface molecules discussed in this paper. For each molecule, the life cycle stages in which they are expressed, and the proposed functions are provided.…”

“…In T. brucei , soluble VSG (sVSG) is shed from the cell surface by GPI-PLC mediated hydrolysis of the GPI-anchor ( Bülow et al, 1989 ; Garrison et al, 2021 ). In addition, membrane form VSG (mfVSG) containing the intact GPI-anchor is released via direct shedding ( Garrison et al, 2021 ). Although GPI-PLC is involved in VSG turnover, its exact function and even localization is still unclear.…”

“…In contrast, the shedding of mfVSG containing an intact GPI anchor might be a direct consequence of the unusual lipid composition of the VSG GPI anchor, which exclusively contains dimyristoyl glycerol ( Ferguson et al, 1988 ). This lipid shows a high off rate from biological membranes at 37°C ( Silvius and Leventis, 1993 ; Silvius and Zuckermann, 1993 ; Garrison et al, 2021 ), which might explain why VSG molecules have been found to integrate into the plasma membrane of erythrocytes ( Rifkin and Landsberger, 1990 ).…”

Turnover of Variant Surface Glycoprotein in Trypanosoma brucei Is Not Altered in Response to Specific Silencing

“…Under normal growth conditions, VSG is very stable, with a half-life ( t 1/2 ) of ~26 h ( 9 – 11 ). Turnover is a bimodal process involving both GPI hydrolysis and direct shedding of VSG with intact GPI anchors ( 11 ).…”

“…Under normal growth conditions, VSG is very stable, with a half-life ( t 1/2 ) of ~26 h ( 9 – 11 ). Turnover is a bimodal process involving both GPI hydrolysis and direct shedding of VSG with intact GPI anchors ( 11 ). VSG is essential for cell viability; RNA interference (RNAi) silencing of expression leads to rapid precytokinesis cell cycle arrest and the global cessation of translation ( 12 , 13 ).…”