Sequences required for the flagellar targeting of an integral membrane protein

NASSER, M; Landfear, Scott M.

doi:10.1016/j.molbiopara.2004.01.009

Cited by 27 publications

(6 citation statements)

References 23 publications

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“…Indeed the only example of differential subcellular localisation of membrane transporters amongst the protozoa is the discrete localisation of hexose transporters to the distinct pellicular and flagellar surface membranes of kinetoplastid parasites. Despite extensive studies, the targeting signal is still poorly understood [171][172][173], as is the possible function of the transporter in the flagellar membrane. Nevertheless, it is possible that some of the many ENT genes in the genomes of some kinetoplastids may encode isoforms with flagellar localisation, where they may contribute to acquisition of purines and pyrimidines.…”

Section: Subcellular Transportersmentioning

confidence: 99%

Purine and pyrimidine transport in pathogenic protozoa: From biology to therapy

2005

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Purine salvage is an essential function for all obligate parasitic protozoa studied to date and most are also capable of efficient uptake of preformed pyrimidines. Much progress has been made in the identification and characterisation of protozoan purine and pyrimidine transporters. While the genes encoding protozoan or metazoan pyrimidine transporters have yet to be identified, numerous purine transporters have now been cloned. All protozoan purine transporter-encoding genes characterised to date have been of the Equilibrative Nucleoside Transporter family conserved in a great variety of eukaryote organisms. However, these protozoan transporters have been shown to be sufficiently different from mammalian transporters to mediate selective uptake of therapeutic agents. Recent studies are increasingly addressing the structure and substrate recognition mechanisms of these vital transport proteins.

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Section: Subcellular Transportersmentioning

confidence: 99%

Purine and pyrimidine transport in pathogenic protozoa: From biology to therapy

2005

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“…For example, the Leishmania enriettii glucose transporter, ISO1, resides primarily in the flagellar membrane, whereas the ISO2 glucose transporter is located in the pellicular plasma membrane. Deletion analyses suggest that the flagellar targeting information for ISO1 does not constitute a simple linear sequence of amino acids but a minimum of two separate sequences in tandem (26). While no such sequence has been identified in Leishmania AQP1, our current observation leads us to speculate that, the N-terminus cytosolic region along with residues in loop D (Fig.…”

Section: Discussionmentioning

confidence: 99%

Functional role of lysine 12 in Leishmania major AQP1

Sharma

Goutam

Srotoswati

et al. 2015

Molecular and Biochemical Parasitology

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Leishmania major aquaglyceroporin (AQP1) is an adventitious metalloid channel that allows the bidirectional movement of arsenite and antimonite. Here we demonstrate that AQP1 is subjected to proteasome-dependent degradation. Treatment of Leishmania promastigotes with the proteasome inhibitor MG132 resulted in increased AQP1 accumulation. Site-directed mutagenesis in AQP1 revealed that alteration of lysine 12 to either alanine or arginine improves protein stability. AQP1 expression is stabilized by mitogen-activated protein kinase 2 (MPK2). Cells expressing a dominant-negative MPK2 mutant exhibited severely reduced AQP1 expression, which could be reversed upon addition of MG132. Interestingly, the dominant- negative MPK2 mutant could not destabilize either AQP1K12A or AQP1K12R. While stabilization of AQP1 by MPK2 leads to its relocalization from flagellum to the entire surface of the parasite, altered AQP1K12A or AQP1K12R was restricted to flagellum only. Our data demonstrate that lysine 12 is targeted for proteasomal degradation of AQP1 and plays an integral role in subcellular localization of AQP1 as well as its interaction with MPK2. This work also raises the possibility that a strategy combining antimonial with a proteasome inhibitor may be an effective combination regimen against diverse forms of leishmaniasis.

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“…Concerning flagellar membrane proteins, two main mechanisms have been documented. The first one concerns the Leishmania glucose transporter, where particular internal epitopes and amino-acids are essential [51], [52]. The second category of proteins must be myristoylated and palmitoylated at their N-termini for reaching the flagellar membrane; it is the case of the T. cruzi FCaBP [53], [54], of the T. brucei Calflagins [55] and of the Leishmania HASPB [56] and SMP-1 [57], [58].…”

Section: Discussionmentioning

confidence: 99%

LdFlabarin, a New BAR Domain Membrane Protein of Leishmania Flagellum

et al. 2013

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During the Leishmania life cycle, the flagellum undergoes successive assembly and disassembly of hundreds of proteins. Understanding these processes necessitates the study of individual components. Here, we investigated LdFlabarin, an uncharacterized L. donovani flagellar protein. The gene is conserved within the Leishmania genus and orthologous genes only exist in the Trypanosoma genus. LdFlabarin associates with the flagellar plasma membrane, extending from the base to the tip of the flagellum as a helicoidal structure. Site-directed mutagenesis, deletions and chimera constructs showed that LdFlabarin flagellar addressing necessitates three determinants: an N-terminal potential acylation site and a central BAR domain for membrane targeting and the C-terminal domain for flagellar specificity. In vitro, the protein spontaneously associates with liposomes, triggering tubule formation, which suggests a structural/morphogenetic function. LdFlabarin is the first characterized Leishmania BAR domain protein, and the first flagellum-specific BAR domain protein.

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Sequences required for the flagellar targeting of an integral membrane protein

Cited by 27 publications

References 23 publications

Purine and pyrimidine transport in pathogenic protozoa: From biology to therapy

Purine and pyrimidine transport in pathogenic protozoa: From biology to therapy

Functional role of lysine 12 in Leishmania major AQP1

LdFlabarin, a New BAR Domain Membrane Protein of Leishmania Flagellum

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