TY  - JOUR
ID  - open1606
UR  - http://www.sciencedirect.com/science/article/pii/S0167488913000116
IS  - 5
A1  - Agarwal, Shruti
A1  - Rastogi, Ruchir
A1  - Gupta, Deepika
A1  - Patel, Nitin
A1  - Raje, Manoj
A1  - Mukhopadhyay, Amitabha
Y1  - 2013/05//
N2  - 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.
PB  - Amsterdam [etc.] Elsevier Pub. Co.
JF  - Biochimica et biophysica acta
VL  - 1833
SN  - 0006-3002
TI  - Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.
SP  - 1065
EP  - 77
ER  -