@article{open1606,
          volume = {1833},
          number = {5},
           month = {May},
          author = {Shruti Agarwal and Ruchir Rastogi and Deepika Gupta and Nitin Patel and Manoj Raje and Amitabha Mukhopadhyay},
           title = {Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.},
       publisher = {Amsterdam [etc.] Elsevier Pub. Co.},
            year = {2013},
         journal = {Biochimica et biophysica acta},
           pages = {1065--77},
             url = {http://crdd.osdd.net/open/1606/},
        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.}
}