Choline induces transcriptional repression and proteasomal degradation of the malarial phosphoethanolamine methyltransferase

William Harold Witola, Choukri Ben Mamoun

Research output: Contribution to journalArticle

Abstract

During its intraerythrocytic life cycle, the malaria parasite Plasmodium falciparum undergoes dramatic metabolic and morphological changes and multiplies to produce up to 36 new daughter parasites. This rapid multiplication of the parasite requires an active synthesis of new membranes. The major component of these membranes, phosphatidylcholine, is synthesized via two metabolic routes, the CDP-choline pathway, which uses host choline as a precursor, and the plant-like serine decarboxylase-phosphoethanolamine methyltransferase (SDPM) pathway, which uses host serine as a precursor. Here we provide evidence indicating that the activity of the SDPM pathway is regulated by the CDP-choline precursor, choline. We show that the phosphoethanolamine methyltransferase, Pfpmt, a critical enzyme in the SDPM pathway, is down-regulated at the transcriptional level as well as targeted for degradation by the proteasome in the presence of choline. Transcript analysis revealed that PfPMT transcription is repressed by choline in a dose-dependent manner. Immunoblotting, pulse-chase experiments, and immunoprecipitation studies demonstrated that Pfpmt degradation occurs not only in wild-type but also in transgenic parasites constitutively expressing Pfpmt. The proteasome inhibitor bortezomib inhibited choline-mediated Pfpmt degradation. These data provide the first evidence for metabolite-mediated transcriptional and proteasomal regulation in Plasmodium and will set the stage for the use of this system for conditional gene and protein expression in this organism.

Original languageEnglish (US)
Pages (from-to)1618-1624
Number of pages7
JournalEukaryotic Cell
Volume6
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

Fingerprint

Methyltransferases
Choline
choline
Serine
Parasites
methyltransferases
Carboxy-Lyases
serine
parasites
degradation
Cytidine Diphosphate Choline
Membranes
proteasome endopeptidase complex
Proteasome Inhibitors
Plasmodium
Falciparum Malaria
Proteasome Endopeptidase Complex
Life Cycle Stages
Phosphatidylcholines
Immunoprecipitation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Microbiology

Cite this

Choline induces transcriptional repression and proteasomal degradation of the malarial phosphoethanolamine methyltransferase. / Witola, William Harold; Mamoun, Choukri Ben.

In: Eukaryotic Cell, Vol. 6, No. 9, 09.2007, p. 1618-1624.

Research output: Contribution to journalArticle

Witola, William Harold; Mamoun, Choukri Ben / Choline induces transcriptional repression and proteasomal degradation of the malarial phosphoethanolamine methyltransferase.

In: Eukaryotic Cell, Vol. 6, No. 9, 09.2007, p. 1618-1624.

Research output: Contribution to journalArticle

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