Proteomics

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Sub-minute phosphoregulation of cell-cycle systems during Plasmodium gamete formation revealed by a high-resolution time course


ABSTRACT: As a first step in the transmission of malaria, Plasmodium parasites ingested by a mosquito must rapidly initiate a gametogenesis process prior to sexual reproduction. The phosphorylation-based signalling mechanisms underlying the initiation of this process remain largely unmapped. We have measured a high-resolution time course of phosphorylation in P. berghei gametocytes during the first minute of gametogenesis to elucidate the scope and dynamics of the response. The data reveals rapid phosphoregulation of microtubule motor proteins and DNA replication initiation proteins within the first 18 s and of DNA replication machinery by 60 s. The data also implicate several protein kinases and phosphatases in the gametogenesis signalling pathway. Through gene knock-out experiments, we verify that the protein kinases CDPK4 and SRPK1 have distinct influences over the phosphorylation of similar downstream targets. Together, the results show that key cell-cycle systems related to both replication and mitosis undergo simultaneous, rapid phosphoregulation.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion

ORGANISM(S): Plasmodium Berghei Anka Mus Musculus (mouse)

DISEASE(S): Malaria

SUBMITTER: James Wright  

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD006266 | Pride | 2017-11-29

REPOSITORIES: Pride

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Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation.

Invergo Brandon M BM   Brochet Mathieu M   Yu Lu L   Choudhary Jyoti J   Beltrao Pedro P   Billker Oliver O  

Cell reports 20171101 7


The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microgametes. The synchronized nature of gametogenesis allowed us to investigate phosphorylation signaling during its first minute in Plasmodium berghei via a high-resolution time course of the phosphoproteome. This  ...[more]

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