creators_name: Agarwal, Shruti
creators_name: Rastogi, Ruchir
creators_name: Gupta, Deepika
creators_name: Patel, Nitin
creators_name: Raje, Manoj
creators_name: Mukhopadhyay, Amitabha
type: article
datestamp: 2015-02-10 11:46:19
lastmod: 2015-02-10 11:46:19
metadata_visibility: show
title: Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.
abstract: 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.
date: 2013-05
date_type: published
publication: Biochimica et biophysica acta
volume: 1833
number: 5
publisher: Amsterdam [etc.] Elsevier Pub. Co.
pagerange: 1065-77
issn: 0006-3002
official_url: http://www.sciencedirect.com/science/article/pii/S0167488913000116
citation:   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