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Multiple short windows of Calcium-Dependent Protein Kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis

CiteULike malaria tags - 11 May 2017 - 10:16am
eLife, Vol. 6 (may 2017), e26524, doi:10.7554/elife.26524

Malaria transmission relies on the production of gametes following ingestion by a mosquito. Here, we show that Ca2+-dependent protein kinase 4 controls three processes essential to progress from a single haploid microgametocyte to the release of eight flagellated microgametes in Plasmodium berghei. A myristoylated isoform is activated by Ca2+ to initiate a first genome replication within twenty seconds of activation. This role is mediated by a protein of the SAPS-domain family involved in S-phase entry. At the same time, CDPK4 is required for the assembly of the subsequent mitotic spindle and to phosphorylate a microtubule-associated protein important for mitotic spindle formation. Finally, a non-myristoylated isoform is essential to complete cytokinesis by activating motility of the male flagellum. This role has been linked to phosphorylation of an uncharacterised flagellar protein. Altogether, this study reveals how a kinase integrates and transduces multiple signals to control key cell-cycle transitions during Plasmodium gametogenesis.
Hanwei Fang, Natacha Klages, Bastien Baechler, Evelyn Hillner, Lu Yu, Mercedes Pardo, Jyoti Choudhary, Mathieu Brochet
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Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase

CiteULike malaria tags - 4 May 2017 - 11:50am
Science Translational Medicine, Vol. 9, No. 387. (26 April 2017), eaad9735, doi:10.1126/scitranslmed.aad9735
Tanya Paquet, Claire Le Manach, Diego Cabrera, Yassir Younis, Philipp Henrich, Tara Abraham, Marcus Lee, Rajshekhar Basak, Sonja Ghidelli-Disse, María Lafuente-Monasterio, Marcus Bantscheff, Andrea Ruecker, Andrew Blagborough, Sara Zakutansky, Anne-Marie Zeeman, Karen White, David Shackleford, Janne Mannila, Julia Morizzi, Christian Scheurer, Iñigo Angulo-Barturen, María Martínez, Santiago Ferrer, Laura Sanz, Francisco Gamo, Janette Reader, Mariette Botha, Koen Dechering, Robert Sauerwein, Anchalee Tungtaeng, Pattaraporn Vanachayangkul, Chek Lim, Jeremy Burrows, Michael Witty, Kennan Marsh, Christophe Bodenreider, Rosemary Rochford, Suresh Solapure, María Jiménez-Díaz, Sergio Wittlin, Susan Charman, Cristina Donini, Brice Campo, Lyn-Marie Birkholtz, Kirsten Hanson, Gerard Drewes, Clemens Kocken, Michael Delves, Didier Leroy, David Fidock, David Waterson, Leslie Street, Kelly Chibale
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Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand

CiteULike malaria tags - 4 May 2017 - 11:33am
Malaria Journal, Vol. 16, No. 1. (28 April 2017), doi:10.1186/s12936-017-1826-8
Rhea Longley, Camila França, Michael White, Chalermpon Kumpitak, Patiwat Sa-angchai, Jakub Gruszczyk, Jessica Hostetler, Anjali Yadava, Christopher King, Rick Fairhurst, Julian Rayner, Wai-Hong Tham, Wang Nguitragool, Jetsumon Sattabongkot, Ivo Mueller
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