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Characterization of an A-kinase anchoring protein-like suggests an alternative way of PKA anchoring in Plasmodium falciparum

Overview of attention for article published in Malaria Journal, April 2016
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Characterization of an A-kinase anchoring protein-like suggests an alternative way of PKA anchoring in Plasmodium falciparum
Published in
Malaria Journal, April 2016
DOI 10.1186/s12936-016-1275-9
Pubmed ID

Kossiwa Bandje, Bernina Naissant, Pascal Bigey, Murielle Lohezic, Marlène Vayssières, Magali Blaud, Laetitia Kermasson, José-Juan Lopez-Rubio, Gordon Langsley, Catherine Lavazec, Philippe Deloron, Anaïs Merckx


The asexual intra-erythrocytic multiplication of the malaria parasite Plasmodium falciparum is regulated by various molecular mechanisms. In eukaryotic cells, protein kinases are known to play key roles in cell cycle regulation and signaling pathways. The activity of cAMP-dependent protein kinase (PKA) depends on A-kinase anchoring proteins (AKAPs) through protein interactions. While several components of the cAMP dependent pathway-including the PKA catalytic and regulatory subunits-have been characterized in P. falciparum, whether AKAPs are involved in this pathway remains unclear. Here, PfAKAL, an open reading frame of a potential AKAP-like protein in the P. falciparum genome was identified, and its protein partners and putative cellular functions characterized. The expression of PfAKAL throughout the erythrocytic cycle of the 3D7 strain was assessed by RT-qPCR and the presence of the corresponding protein by immunofluorescence assays. In order to study physical interactions between PfAKAL and other proteins, pull down experiments were performed using a recombinant PfAKAL protein and parasite protein extracts, or with recombinant proteins. These interactions were also tested by combining biochemical and proteomic approaches. As phosphorylation could be involved in the regulation of protein complexes, both PfAKAL and Pf14-3-3I phosphorylation was studied using a radiolabel kinase activity assay. Finally, to identify a potential function of the protein, PfAKAL sequence was aligned and structurally modeled, revealing a conserved nucleotide-binding pocket; confirmed by qualitative nucleotide binding experiments. PfAKAL is the first AKAP-like protein in P. falciparum to be identified, and shares 23 % sequence identity with the central domain of human AKAP18δ. PfAKAL is expressed in mature asexual stages, merozoites and gametocytes. In spite of homology to AKAP18, biochemical and immunochemical analyses demonstrated that PfAKAL does not interact directly with the P. falciparum PKA regulatory subunit (PfPKA-R), but instead binds and colocalizes with Pf14-3-3I, which in turn interacts with PfPKA-R. In vivo, these different interactions could be regulated by phosphorylation, as PfPKA-R and Pf14-3-3I, but not PfAKAL, are phosphorylated in vitro by PKA. Interestingly, PfAKAL binds nucleotides such as AMP and cAMP, suggesting that this protein may be involved in the AMP-activated protein kinase (AMPK) pathway, or associated with phosphodiesterase activities. PfAKAL is an atypical AKAP that shares common features with human AKAP18, such as nucleotides binding. The interaction of PfAKAL with PfPKA-R could be indirectly mediated through a join interaction with Pf14-3-3I. Therefore, PfPKA localization could not depend on PfAKAL, but rather involves other partners.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 29%
Student > Bachelor 5 24%
Student > Master 2 10%
Researcher 2 10%
Professor 1 5%
Other 1 5%
Unknown 4 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 29%
Medicine and Dentistry 4 19%
Agricultural and Biological Sciences 3 14%
Immunology and Microbiology 2 10%
Economics, Econometrics and Finance 1 5%
Other 1 5%
Unknown 4 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 May 2016.
All research outputs
of 7,651,252 outputs
Outputs from Malaria Journal
of 2,579 outputs
Outputs of similar age
of 266,283 outputs
Outputs of similar age from Malaria Journal
of 153 outputs
Altmetric has tracked 7,651,252 research outputs across all sources so far. This one has received more attention than most of these and is in the 56th percentile.
So far Altmetric has tracked 2,579 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,283 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.
We're also able to compare this research output to 153 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.