The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner.
Apicomplexan parasites possess a unique cortical cytoskeleton structure composed of intermediate filaments. Its building blocks are provided by a conserved family of proteins named alveolins. The core alveolin structure is made up of tandem repeat sequences, thought to be responsible for the filamentous properties of these proteins. A subset of alveolins also possess conserved motifs composed of three closely spaced cysteine residues situated near the ends of the polypeptides. The roles of these cysteine motifs and their contribution to alveolin function remains poorly understood. The sporozoite-expressed IMC1a is unique within the Plasmodium alveolin family in having conserved cysteine motifs at both termini. Using transgenic Plasmodium berghei parasites, we show in this structure-function analysis that mutagenesis of the amino- or carboxy-terminal cysteine motif causes marked reductions in IMC1a protein levels in the parasite, which are accompanied by partial losses of sporozoite shape and infectivity. Our findings give new insight into alveolin function, identifying a dose-dependent effect of alveolin depletion on sporozoite size and infectivity, and vital roles of the terminal cysteine motifs in maintaining alveolin stability in the parasite.
Pathogen Molecular Biology Department, London School of Hygiene & Tropical Medicine, Keppel street, London WC1E 7HT, United Kingdom.
Fatimah S
FS
Al-Khattaf
Pathogen Molecular Biology Department, London School of Hygiene & Tropical Medicine, Keppel street, London WC1E 7HT, United Kingdom.
Annie Z
AZ
Tremp
Pathogen Molecular Biology Department, London School of Hygiene & Tropical Medicine, Keppel street, London WC1E 7HT, United Kingdom.
Amira
A
El-Houderi
Pathogen Molecular Biology Department, London School of Hygiene & Tropical Medicine, Keppel street, London WC1E 7HT, United Kingdom. Electronic address: Johannes.Dessens@lshtm.ac.uk.
Johannes T
JT
Dessens
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine; D005260:Female; D008288:Malaria / Q000469:parasitology; D051379:Mice; D009024:Morphogenesis; D009154:Mutation; D010641:Phenotype; D010961:Plasmodium / Q000502:physiology*; D000072417:Protein Domains / Q000235:genetics; D055550:Protein Stability; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D034101:Sporozoites / Q000254:growth & development*
D015800:Protozoan Proteins; D003545:Cysteine
Alveolin; Cytoskeleton; Intermediate filament; Palmitoylation; Plasmodium berghei; Sporozoite
Mol Cell Proteomics. 2010 Jul;9(7):1437-48
20332084
Parasitol Today. 2000 Oct;16(10):427-33
11006474
Annu Rev Biochem. 2004;73:749-89
15189158
J Biol Chem. 2008 Oct 10;283(41):27604-11
18650444
Mol Biochem Parasitol. 2001 Jul;115(2):257-68
11420112
Nature. 2002 Oct 3;419(6906):520-6
12368866
Nature. 2002 Oct 3;419(6906):537-42
12368870
Antioxid Redox Signal. 2014 Jul 20;21(3):438-56
24483706
Int J Parasitol. 2009 Jan;39(2):153-62
19028497
Parasitol Res. 2015 Feb;114(2):631-9
25475193
J Biol Chem. 2002 Oct 25;277(43):41240-6
12177058
Mol Biol Evol. 2008 Jun;25(6):1219-30
18359944
J Proteome Res. 2013 Sep 6;12(9):4028-45
23914800
Mol Biochem Parasitol. 2010 Mar;170(1):49-53
19932717
Anal Biochem. 2009 Oct 1;393(1):129-31
19523435
Nat Commun. 2011 Nov 29;2:565
22127061
Microbiol Mol Biol Rev. 2002 Mar;66(1):21-38; table of contents
11875126
Science. 2005 Jan 7;307(5706):82-6
15637271
Eukaryot Cell. 2013 Jun;12(6):932-40
23606287
Mol Cell Proteomics. 2011 May;10(5):M110.001636
20943600
J Biol Chem. 2011 Feb 18;286(7):5383-91
21098480
Curr Biol. 2013 May 20;23(10):R431-5
23701681
PLoS One. 2012;7(7):e41409
22844474
Trends Parasitol. 2003 Mar;19(3):135-43
12643997
Parasitol Res. 2014 Nov;113(11):4177-88
25185663
Nat Rev Mol Cell Biol. 2007 Jan;8(1):74-84
17183362
J Cell Biol. 2004 Nov 8;167(3):425-32
15533999
EMBO J. 1999 Nov 15;18(22):6221-7
10562534
Methods. 1997 Oct;13(2):134-47
9405197
Cell Host Microbe. 2011 Oct 20;10(4):410-9
22018241
Cell Microbiol. 2011 Jan;13(1):18-31
20698859
Cell Host Microbe. 2012 Aug 16;12(2):246-58
22901544
PLoS Pathog. 2015 May 27;11(5):e1004905
26018192