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* E-mail: christian.doerig@monash.edu
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1
INSERM-EPFL Joint Laboratory, Global
Health Institute, Ecole Polytechnique
Fédérale de Lausanne, GHI-SV-EPFL
Station 19, CH-1015 Lausanne,
Switzerland
2
INSERM U609, Wellcome Centre for
Molecular Parasitology, University of
Glasgow, Glasgow G12 8TA,
Scotland, UK
3
Department of Microbiology, Monash
University, Wellington Road, Clayton, VIC
3800, Australia.
4
Institut Curie, 26 Rue d’Ulm, 75248 PARIS
cedex 05, France
5
Biochemistry, University of Kwazulu-Natal,
PB X01 Scottsville, South Africa
6
Dept. of Molecular Biology and
Microbiology, University of Central Florida,
12722 Research Parkway Orlando
FL32826, USA
7
Special Centre for Molecular Medicine,
Jawaharlal Nehru University, New
Delhi-110067, India
8
Departments of Medicine and Molecular
Microbiology, Howard Hughes Medical
Institute, Washington University Box 8230,
660 S. Euclid Ave, St. Louis, MO 63110, USA
9
Department of Biochemistry and
Molecular Biology, Bio21 Molecular
Science and Biotechnology Institute, The
University of Melbourne, Parkville, 3010,
Victoria, Australia
10
Australian Research Council Centre of
Excellence for Coherent X-ray Science,
The University of Melbourne, Parkville,
3010, Victoria, Australia
+
Present address: Inserm U665, Institut
National de Transfusion sanguine, 6,
rue Alexandre Cabanel, 75739 Paris
Cedex 5, France
Dominique Dorin-Semblat
1,2,+
,
Teresa Gil Carvalho
3
,
Marie-Paule Nivez
2
,
Jean Halbert
1,2
,
Patrick Poullet
4
,
Jean-Philippe Semblat
1,2,+
,
Dean Goldring
5
,
Debopam Chakrabarti
6
,
Parul Mehra
7
,
Suman Dhar
7
,
May M.Paing
8
,
Daniel E. Goldberg
8
,
Paul J. McMillan
9,10
,
Leann Tilley
9,10
,
Christian Doerig
1,2,3
*
Received 24 January 2013
Accepted 24 February 2013
Abstract
Malaria parasites multiply in human erythrocytes through schizogony, a
process characterised by nuclear divisions in the absence of cytokinesis,
leading to the formation of a multinucleated schizont from which individual
daughter cells are subsequently generated. Here, we provide evidence
that parasites lines lacking Pfcrk-5, an atypical cyclin-dependent kinase,
display a reduced parasitemia growth rate linked to a decrease in the
number of daughter nuclei produced by each schizont. We show that
in vitro activity of recombinant Pfcrk-5 is indeed cyclin-dependent, and
that the enzyme localises to the nuclear periphery. Thus, Pfcrk-5 is part
of a regulatory pathway that mediates the proliferation rate of Plasmodium
falciparum through the control of nuclear divisions during schizogony.
Keywords
*`JSPUKLWLUKLU[ RPUHZL Plasmodium falciparum 7MJYR *LSS J`JSL 4HSHYPH
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