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Leishmania species: evidence for transglutaminase activity and its role in parasite proliferation
Authors:Brobey Reynolds K B  Soong Lynn
Affiliation:Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Abstract:Albeit transglutaminase (TGase) activity has been reported to play crucial physiological roles in several organisms including parasites; however, there was no previous report(s) whether Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in Leishmania parasites by using labeled polyamine that becomes conjugated into protein substrates. The parasite enzyme was about 2- to 4-fold more abundant in Old World species than in New World ones. In L. amazonensis, comparable TGase activity was found in both promastigotes and amastigotes. TGase activity in either parasite stage was optimal at the basic pH, but the enzyme in amastigote lysates was more stable at higher temperatures (37-55 degrees C) than that in promastigote lysates. Leishmania TGase differs from mouse macrophage (M Phi) TGase in two ways: (1) the parasite enzyme is Ca(2+)-independent, whereas the mammalian TGase depends on the cation for activity, and (2) major protein substrates for L. amazonensis TGase were found within the 50-75 kDa region, while those for the M Phi TGase were located within 37-50 kDa. The potential contribution of TGase-catalyzed reactions in promastigote proliferation was supported by findings that standard inhibitors of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate synthase and leishmanolysin (gp63) were identified as possible endogenous substrates for L. amazonensis TGase, implying a role for TGase in parasite growth, development, and survival.
Keywords:Leishmania   Trypanosomatid   Parasite   Promastigote   Amastigote   Western blot   Inhibition   Transglutaminase (EC 2.3.2.13)   Glycoconjugates   TGase, transglutaminase   MDC, monodansylcadaverine   DDC, didansylcadaverine   CS, cystamine   IodoA, iodoacetamide   FC, fluorescein cadaverine   PTM, posttranslational modification   MES, 2-[N-morpholino]ethanesulfonic acid   MΦ, macrophage   BCA, bicinchonic acid
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