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Blocking variant surface glycoprotein synthesis alters ERES/ Golgi homeostasis in Trypanosoma brucei

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Title: Blocking variant surface glycoprotein synthesis alters ERES/ Golgi homeostasis in Trypanosoma brucei
Authors: Ooi, C-P
Smith, TK
Gluenz, E
Wand, NV
Vaughan, S
Rudenko, G
Item Type: Journal Article
Abstract: The predominant secretory cargo of bloodstream form Trypanosoma brucei is Variant Surface Glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre/cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post/mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of ER exit sites (ERES) in post/mitotic cells dropped from (3.9 ± 0.6) to (2.7 ± 0.1) eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and GPI/anchor biosynthesis were relatively unaffected, except for the level of sphingomyelin which increased. However, both ER and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans/face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, i.e. VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei including the ERES and Golgi.
Issue Date: 1-Jun-2018
Date of Acceptance: 28-Feb-2018
URI: http://hdl.handle.net/10044/1/57724
DOI: https://dx.doi.org/10.1111/tra.12561
ISSN: 1398-9219
Publisher: Wiley
Start Page: 391
End Page: 405
Journal / Book Title: Traffic
Volume: 19
Issue: 6
Copyright Statement: © 2018 The Authors. Traffic published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any me dium, provided the original work is properly cited.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 095161/Z/10/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
ER exit site
Golgi biogenesis
membrane metabolism
secretory pathway
Trypanosoma brucei
variant surface glycoprotein
BLOOD-STREAM-FORM
UNFOLDED PROTEIN RESPONSE
GPI-ANCHORED PROTEINS
PLANT GOLGI-APPARATUS
AFRICAN TRYPANOSOMES
POSTTRANSLATIONAL MODIFICATION
INTRACELLULAR-TRANSPORT
SPHINGOLIPID SYNTHESIS
SECRETORY PATHWAY
DRUG TARGET
0601 Biochemistry And Cell Biology
Developmental Biology
Publication Status: Published
Online Publication Date: 2018-03-13
Appears in Collections:Faculty of Natural Sciences



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