Abstract:
: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.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
Sharma M,Mandal G,Mandal S,Bhattacharjee H,Mukhopadhyay Rdoi
10.1016/j.molbiopara.2015.07.005subject
Has Abstractpub_date
2015-06-01 00:00:00pages
139-45issue
2eissn
0166-6851issn
1872-9428pii
S0166-6851(15)30016-5journal_volume
201pub_type
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
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journal_title:Molecular and biochemical parasitology
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pub_type: 杂志文章
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journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章,评审
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更新日期:2006-07-01 00:00:00