Vital role for the Plasmodium actin capping protein (CP) beta-subunit in motility of malaria sporozoites.
Summary Successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. Sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. A unique feature of this motor machinery is the presence of very short subpellicular actin filaments. Therefore, F-actin stabilizing proteins likely play a central role in parasite locomotion. Here, we investigated the role of the Plasmodium berghei actin capping protein (PbCP), an orthologue of the heterodimeric regulator of filament barbed end growth, by reverse genetics. Parasites containing a deletion of the CP beta-subunit developed normally during the pathogenic erythrocytic cycle. However, due to reduced ookinete motility, mutant parasites form fewer oocysts and sporozoites in the Anopheles vector. These sporozoites display a vital deficiency in forward gliding motility and fail to colonize the mosquito salivary glands, resulting in complete attenuation of life cycle progression. Together, our results show that the CP beta-subunit exerts an essential role in the insect vector before malaria transmission to the mammalian host. The vital role is restricted to fast locomotion, as displayed by Plasmodium sporozoites.
Ganter
Markus
M
Department of Parasitology, Heidelberg University School of Medicine, 69120 Heidelberg, Germany.
Schüler
Herwig
H
Matuschewski
Kai
K
D051344:Actin Capping Proteins / Q000235:genetics / Q000502:physiology*; D000199:Actins / Q000378:metabolism; D000825:Animal Structures / Q000469:parasitology; D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D017353:Gene Deletion; D008124:Locomotion; D008958:Models, Molecular; D010962:Plasmodium berghei / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D012469:Salivary Glands / Q000469:parasitology; D034101:Sporozoites / Q000502:physiology*
D051344:Actin Capping Proteins; D000199:Actins; D021122:Protein Subunits; D015800:Protozoan Proteins
Science. 2004 Apr 9;304(5668):248-53
15073368
J Exp Med. 1979 Jan 1;149(1):172-84
105074
Mol Biol Cell. 1993 May;4(5):459-68
8334302
EMBO J. 2003 Apr 1;22(7):1529-38
12660160
BMC Genomics. 2005 Dec 12;6:179
16343347
J Cell Biol. 1994 Jul;126(2):403-12
7518465
Cell. 1995 May 19;81(4):591-600
7758113
J Muscle Res Cell Motil. 1998 Aug;19(6):639-46
9742448
Nature. 1999 Oct 7;401(6753):613-6
10524632
Trends Parasitol. 2006 Apr;22(4):146-7
16500149
Cell Microbiol. 2006 Oct;8(10):1547-56
16984410
PLoS Pathog. 2007 Dec 28;3(12):e195
18166078
Trends Biochem Sci. 2004 Aug;29(8):418-28
15362226
J Parasitol. 1975 Feb;61(1):43-50
1090717
J Cell Biol. 1992 Jun;117(5):1067-76
1315784
Trends Cell Biol. 2004 Oct;14(10):528-32
15450974
Electrophoresis. 1997 Dec;18(15):2714-23
9504803
Methods Mol Med. 2002;72:317-31
12125129
FEBS Lett. 2005 Jan 31;579(3):655-60
15670824
Traffic. 2006 Nov;7(11):1433-9
17010119
Cell Host Microbe. 2008 Mar 13;3(3):188-98
18329618
Curr Mol Med. 2006 Mar;6(2):137-40
16515506
J Cell Biol. 2003 Sep 15;162(6):1079-88
12975351
J Biol Chem. 2002 Nov 1;277(44):41948-53
12177071
Cell Microbiol. 2008 Feb;10(2):452-64
17944961
Mol Cell. 2003 Apr;11(4):885-94
12718875
J Cell Biol. 1996 Jun;133(6):1293-305
8682865
PLoS Pathog. 2007 Mar;3(3):e30
17335349
Science. 2002 Oct 25;298(5594):837-40
12399593
Mol Biol Cell. 2006 Feb;17(2):895-906
16319175
EMBO J. 2006 Nov 29;25(23):5626-33
17110933
J Cell Sci. 2003 Jan 1;116(Pt 1):39-49
12456714
J Biol Chem. 1995 Sep 15;270(37):21472-9
7665558
Cell Motil Cytoskeleton. 1999;42(1):73-81
9915586
J Mol Biol. 2005 May 27;349(1):113-25
15876372
Mol Biochem Parasitol. 2006 Jan;145(1):60-70
16242190
J Biol Chem. 2007 Aug 10;282(32):23005-9
17576764
Nat Rev Microbiol. 2006 Aug;4(8):621-8
16845432
Mol Biochem Parasitol. 1998 Jun 1;93(2):295-308
9662713
Curr Opin Microbiol. 2007 Dec;10(6):547-53
18006365
Subcell Biochem. 2008;47:110-20
18512346
Cell. 2004 Aug 6;118(3):363-73
15294161
Mol Biol Cell. 2003 Dec;14(12):4947-57
14595113
Int Rev Cell Mol Biol. 2008;267:183-206
18544499