A nucleolar AAA-NTPase is required for parasite division

Suvorova ES, Radke JB, Ting LM, Vinayak S, Alvarez CA, Kratzer S, Kim K, Striepen B, White MW.

Source

Departments of Molecular Medicine & Global Health, University of South Florida, Tampa, FL 33612.

Abstract

Apicomplexa division involves several distinct phases shared with other eukaryote cell cycles including a gap period (G1) prior to chromosome synthesis, although how progression through the parasite cell cycle is controlled is not understood. Here we describe a cell cycle mutant that reversibly arrests in the G1 phase. The defect in this mutant was mapped by genetic complementation to a gene encoding a novel AAA-ATPase/CDC48 family member called TgNoAP1. TgNoAP1 is tightly regulated and expressed in the nucleolus during the G1/S phases. A tyrosine to a cysteine change upstream of the second AAA+ domain in the temperature sensitive TgNoAP1 allele leads to conditional protein instability, which is responsible for rapid cell cycle arrest and a primary defect in 28S rRNA processing as confirmed by knock-in of the mutation back into the parent genome. The interaction of TgNoAP1 with factors of the snoRNP and R2TP complexes indicates this protein has a role in pre-rRNA processing. This is a novel role for a cdc48-related chaperone protein and indicates that TgNoAP1 may be part of a dynamic mechanism that senses the health of the parasite protein machinery at the initial steps of ribosome biogenesis and conveys that information to the parasite cell cycle checkpoint controls.
This article is protected by copyright. All rights reserved.

KEYWORDS:

AAA-ATPase, Apicomplexa, G1 phase, Toxoplasma gondii, cell cycle, nucleolus, replication

PMID:: 23964771; [PubMed - as supplied by publisher]

The Toxoplasma Blog

Monday, August 26, 2013