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Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.
 
Creator Agarwal, Shruti
Rastogi, Ruchir
Gupta, Deepika
Patel, Nitin
Raje, Manoj
Mukhopadhyay, Amitabha
 
Description Leishmania is auxotroph for heme. Previously, we have shown that Leishmania acquire heme from the degradation of endocytosed hemoglobin via a specific receptor located in the flagellar pocket. Here, we report the cloning and expression of clathrin heavy chain from Leishmania (Ld-CHC) and provide evidences that Ld-CHC is localized in flagellar pocket and regulates Hb-endocytosis in Leishmania. Kinetic analysis of Hb trafficking in GFP-Ld-CHC overexpressed Leishmania reveals that Hb is internalized through Ld-CHC coated region and remains associated with Ld-CHC containing vesicles at early time points of internalization and subsequently starts dissociating from Hb-containing vesicles at later time points indicating that clathrin-coating and uncoating regulate Hb trafficking in Leishmania. Interestingly, overexpression of dominant negative mutant of clathrin heavy chain of Leishmania (GFP-Ld-CHC-Hub) blocks the Hb internalization and causes severe growth defect in parasite. Moreover, we have shown that chlorpromazine, a pharmacological agent, blocks Hb internalization in Leishmania by depolymerizing Ld-CHC and thereby inhibits the growth of the parasites. Taken together, our results have shown that Hb endocytosis in Leishmania is a clathrin dependent process and is essential for the survival of the parasites.
 
Publisher Amsterdam [etc.] Elsevier Pub. Co.
 
Date 2013-05
 
Type Article
NonPeerReviewed
 
Relation http://www.sciencedirect.com/science/article/pii/S0167488913000116
http://crdd.osdd.net/open/1606/
 
Identifier Agarwal, Shruti and Rastogi, Ruchir and Gupta, Deepika and Patel, Nitin and Raje, Manoj and Mukhopadhyay, Amitabha (2013) Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania. Biochimica et biophysica acta, 1833 (5). pp. 1065-77. ISSN 0006-3002