title: Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.
creator: Agarwal, Shruti
creator: Rastogi, Ruchir
creator: Gupta, Deepika
creator: Patel, Nitin
creator: Raje, Manoj
creator: 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
type: NonPeerReviewed
relation: http://www.sciencedirect.com/science/article/pii/S0167488913000116
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     
relation: http://crdd.osdd.net/open/1606/