Inositol polyphosphate multikinase regulation of Trypanosoma brucei life stage development.

Abstract:

:Many cellular processes change during the Trypanosoma brucei life cycle as this parasite alternates between the mammalian host and tsetse fly vector. We show that the inositol phosphate pathway helps regulate these developmental changes. Knockdown of inositol polyphosphate multikinase (IPMK), which phosphorylates Ins(1,4,5)P3 and Ins(1,3,4,5)P4, resulted in changes in bloodstream forms that are characteristic of insect stage procyclic forms. These changes include expression of the procyclic surface coat, up-regulation of RNA-binding proteins that we show to regulate stage-specific transcripts, and activation of oxidative phosphorylation with increased ATP production in bloodstream forms. These changes were accompanied by development of procyclic morphology, which also occurred by the expression of a catalytically inactive IPMK, implying that regulation of these processes entails IPMK activity. Proteins involved in signaling, protein synthesis and turnover, and metabolism were affinity-enriched with the IPMK substrate or product. Developmental changes associated with IPMK knockdown or catalytic inactivation reflected processes that are enriched with inositol phosphates, and chemical and genetic perturbation of these processes affected T. brucei development. Hence, IPMK helps regulate T. brucei development, perhaps by affecting inositol phosphate interactions with proteins of the regulatory network that controls energy metabolism and development.

journal_name

Mol Biol Cell

authors

Cestari I,Anupama A,Stuart K

doi

10.1091/mbc.E17-08-0515

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

1137-1152

issue

9

eissn

1059-1524

issn

1939-4586

pii

mbc.E17-08-0515

journal_volume

29

pub_type

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