The Plasmodium falciparum heat shock protein 40, Pfj4, associates with heat shock protein 70 and shows similar heat induction and localisation patterns

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Background: Malaria pathogenesis depends on intricate functioning of ER secretory pathway; however, it lacks canonical UPR machinery to respond to ER stress. Results: Malaria parasite fails to induce ER chaperones and converts to gametocytes upon ER stress. Conclusion: Malaria parasite escapes ER stress by switching to the sexual stage. Significance: ER stress may serve as a physiological cue for parasites to undergo gametocytogenesis.

Section: Bioinformatics Analysis Reveals Lack Of Upr Machinery In Psupporting

confidence: 79%

Endoplasmic Reticulum Stress Triggers Gametocytogenesis in the Malaria Parasite

Chaubey

Grover

Tatu

2014

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“…6). To confirm this, we also stained the cells using anti-HSP70 antibody, a commonly used cytosolic marker (43). The merged image shows co-localization, indicating that the expressed HA-tagged PfGMD and PfFS are localized in the cytosol of P. falciparum through the different stages of the parasite asexual life cycle.…”

Section: Pfgmd and Pffs Are Expressed During P Falciparum Intraerythmentioning

confidence: 85%

Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum

Sanz

Bandini

Ospina

et al. 2013

Background: GDP-fucose and other sugar nucleotide biosynthetic pathways are conserved in the P. falciparum genome. Results: These pathways are active in the intraerythrocytic life cycle of the parasite. Conclusion:The parasite biosynthesizes GDP-fucose and other sugar nucleotides not related to the glycosylphosphatidylinositol structures Significance: Their presence strongly suggests that they are involved in the biosynthesis of glycans not yet characterized.

“…Several other reports have analyzed the effects of overexpression of the J domains of cognate or non-cognate JDPs in related/divergent model systems (13,62,63), but rarely has the specific impact of the JDP substrate-binding domain been investigated. Our data, together with those of others, reveal novel insights into the biology of DnaJ family proteins.…”

Section: Discussionmentioning

confidence: 99%

The Mammalian Hsp40 ERdj3 Requires Its Hsp70 Interaction and Substrate-binding Properties to Complement Various Yeast Hsp40-dependent Functions

Vembar

Jin

Brodsky

et al. 2009

Heat shock proteins of 70 kDa (Hsp70s) and their J domaincontaining Hsp40 cofactors are highly conserved chaperone pairs that facilitate a large number of cellular processes. The observation that each Hsp70 partners with many J domain-containing proteins (JDPs) has led to the hypothesis that Hsp70 function is dictated by cognate JDPs. If this is true, one might expect highly divergent Hsp70-JDP pairs to be unable to function in vivo. However, we discovered that, when a yeast cytosolic JDP, Ydj1, was targeted to the mammalian endoplasmic reticulum (ER), it interacted with the ER-lumenal Hsp70, BiP, and bound to BiP substrates. Conversely, when a mammalian ERlumenal JDP, ERdj3, was directed to the yeast cytosol, it rescued the temperature-sensitive growth phenotype of yeast-containing mutant alleles in two cytosolic JDPs, HLJ1 and YDJ1, and activated the ATP hydrolysis rate of Ssa1, the yeast cytosolic Hsp70 that partners with Hlj1 and Ydj1. Surprisingly, ERdj3 mutants that were compromised for substrate binding were unable to rescue the hlj1ydj1 growth defect even though they stimulated the ATPase activity of Ssa1. Yet, J domain mutants of ERdj3 that were defective for interaction with Ssa1 restored the growth of hlj1ydj1 yeast. Taken together, these data suggest that the substrate binding properties of certain JDPs, not simply the formation of unique Hsp70-JDP pairs, are critical to specify in vivo function. Hsp70s3 constitute a highly conserved family of molecular chaperones that are found in all organisms and in all cellular organelles. Due to their ability to bind to unfolded regions on nascent polypeptides or unassembled subunits of heteromeric complexes in a nucleotide-dependent manner, these chaperones play critical roles in diverse cellular processes (1, 2). Two distinct sets of cofactors tightly monitor Hsp70 action by regulating ATPase activity (3, 4): J domain-containing proteins (JDPs) of the Hsp40/DnaJ family and nucleotide exchange factors. The highly conserved ϳ70-amino acid J domain of JDPs contacts the nucleotide-binding domain of Hsp70 and enhances ATPase activity by inducing a conformational change (5, 6). This leads to enhanced binding of Hsp70s to substrates. Moreover, some JDPs directly bind to unfolded regions on substrate proteins through their substrate-binding domain and deliver the unfolded protein to the ATP-bound form of their Hsp70 partner (7, 8), whereas others contain atypical domains that specify exclusive functions (9, 10). The nucleotide exchange factors, on the other hand, release bound ADP, which triggers ATP rebinding and subsequent substrate release from the Hsp70.The JDPs can be classified into three groups (11, 12): (i) type I JDPs are most similar to DnaJ and contain a J domain followed by a glycine/phenylalanine-rich region and a cysteine-rich region with four repeats of a CXXCXGXG-type zinc finger; (ii) type II JDPs lack the cysteine-rich region and are unable to coordinate Zn 2ϩ ; and (iii) type III JDPs only have the J domain in common with DnaJ. Notably, the number o...