Plasmodium sporozoite excystation involves local breakdown of the oocyst capsule.

Plasmodium oocysts develop on the abluminal side of the mosquito midgut in relatively small numbers. Oocysts possess an extracellular cell wall-the capsule-to protect them from the insect's haemolymph environment. To further maximise transmission, each oocyst generates hundreds of sporozoites through an asexual multiplication step called sporogony.

NAD(P) transhydrogenase isoform distribution provides insight into apicomplexan evolution.

Membrane-located NAD(P) transhydrogenase (NTH) catalyses reversible hydride ion transfer between NAD(H) and NADP(H), simultaneously translocating a proton across the membrane. The enzyme is structurally conserved across prokaryotes and eukaryotes. In heterotrophic bacteria NTH proteins reside in the cytoplasmic membrane, whereas in animals they localise in the mitochondrial inner membrane.

Plasmodium berghei oocysts possess fatty acid synthesis and scavenging routes.

Malaria parasites carry out fatty acid synthesis (FAS) in their apicoplast organelle via a bacterially related (type II) enzymatic pathway. In the vertebrate host, exoerythrocytic Plasmodium stages rely on FAS, whereas intraerythrocytic stages depend on scavenging FA from their environment. In the mosquito, P.

leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development.

Protein phosphatase 1 (PP1) is a key enzyme for development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors.

Crystalloids: Fascinating Parasite Organelles Essential for Malaria Transmission.

Crystalloids are malaria parasite organelles exclusive to the ookinete and young oocyst life stages that infect the mosquito. The organelles have key roles in sporozoite development and infectivity but the way this is facilitated on a molecular level remains poorly understood. Recent discoveries have shed new light on these processes.

Plasmodium berghei LAPs form an extended protein complex that facilitates crystalloid targeting and biogenesis.

Passage of malaria parasites through mosquitoes involves multiple developmental transitions, from gametocytes that are ingested with the blood meal, through to sporozoites that are transmitted by insect bite to the host. During the transformation from gametocyte to oocyst, the parasite forms a unique transient organelle named the crystalloid, which is involved in sporozoite formation. In Plasmodium berghei, a complex of six LCCL domain-containing proteins (LAPs) reside in the crystalloid and are required for its biogenesis.

NAD(P) transhydrogenase has vital non-mitochondrial functions in malaria parasite transmission.

Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form (NADP) are vital for cell function in all organisms and form cofactors to a host of enzymes in catabolic and anabolic processes. NAD(P) transhydrogenases (NTHs) catalyse hydride ion transfer between NAD(H) and NADP(H). Membrane-bound NTH isoforms reside in the cytoplasmic membrane of bacteria, and the inner membrane of mitochondria in metazoans, where they generate NADPH.

Distinct Functional Contributions by the Conserved Domains of the Malaria Parasite Alveolin IMC1h.

Invasive, motile life cycle stages (zoites) of apicomplexan parasites possess a cortical membrane skeleton composed of intermediate filaments with roles in zoite morphogenesis, tensile strength and motility. Its building blocks include a family of proteins called alveolins that are characterized by conserved "alveolin" domains composed of tandem repeat sequences. A subset of alveolins possess additional conserved domains that are structurally unrelated and the roles of which remain unclear.

Dysregulated gene expression in oocysts of Plasmodium berghei LAP mutants.

Malaria parasite oocysts generate sporozoites by a process termed sporogony. Essential for successful sporogony of Plasmodium berghei in Anopheles stephensi mosquitoes is a complex of six LCCL lectin domain adhesive-like proteins (LAPs). LAP null mutant oocysts undergo growth and mitosis but fail to form sporozoites.

The Plasmodium LAP complex affects crystalloid biogenesis and oocyst cell division.

Malaria parasite oocysts located on the mosquito midgut generate sporozoites by a process called sporogony. Plasmodium berghei parasites express six LCCL lectin domain adhesive-like proteins (LAPs), which operate as a complex and share a localisation in the crystalloid - an organelle found in the ookinete and young oocyst. Depletion of LAPs prevents crystalloid formation, increases oocyst growth, and blocks sporogony.

LCCL protein complex formation in Plasmodium is critically dependent on LAP1.

Successful sporogony of Plasmodium berghei in vector mosquitoes requires expression of a family of six modular proteins named LCCL lectin domain adhesive-like proteins (LAPs). The LAPs share a subcellular localization in the crystalloid, a unique parasite organelle that forms during ookinete development. Here, LAP interactions in P.

Palmitoylation of Plasmodium alveolins promotes cytoskeletal function.

S-palmitoylation is a post-translational lipid modification that is widespread among Plasmodium proteins and essential for parasite development. Little is known about the contribution of palmitoylation to the function of individual parasite molecules and structures. Alveolins are major components of the subpellicular network (SPN), a cortical cytoskeleton primarily involved in providing mechanical strength to the cell.

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.

Biogenesis of the crystalloid organelle in Plasmodium involves microtubule-dependent vesicle transport and assembly.

Malaria parasites possess unique subcellular structures and organelles. One of these is the crystalloid, a multivesicular organelle that forms during the parasite's development in vector mosquitoes. The formation and function of these organelles remain poorly understood.

Plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.

The invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. The pellicle is characterised by a double-layered 'inner membrane complex' (IMC) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (SPN). The SPN consists of intermediate filaments, whose major constituents include a family of proteins called alveolins.

Distinct temporal recruitment of Plasmodium alveolins to the subpellicular network.

The zoite stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle, which is defined by a double membrane layer named the inner membrane complex (IMC). The IMC is supported by a cytoskeleton of intermediate filaments, termed the subpellicular network (SPN). Plasmodium IMC1 proteins, or alveolins, make up a conserved family of structurally related proteins that comprise building blocks of the SPN.

Morphogenesis of Plasmodium zoites is uncoupled from tensile strength.

A shared feature of the motile stages (zoites) of malaria parasites is a cortical cytoskeletal structure termed subpellicular network (SPN), thought to define and maintain cell shape. Plasmodium alveolins comprise structural components of the SPN, and alveolin gene knockout causes morphological abnormalities that coincide with markedly reduced tensile strength of the affected zoites, indicating the alveolins are prime cell shape determinants. Here, we characterize a novel SPN protein of Plasmodium berghei ookinetes and sporozoites named G2 (glycine at position 2), which is structurally unrelated to alveolins.

Translational repression controls temporal expression of the Plasmodium berghei LCCL protein complex.

Plasmodium LCCL proteins comprise a family of six proteins that function as a protein complex and have essential roles in sporozoite transmission. In Plasmodium berghei, family members PbLAP1, PbLAP2 and PbLAP3 have been shown to be expressed in gametocytes and, following gametogenesis and fertilization, to be targeted to distinctive multivesicular organelles termed crystalloids that form in the ookinete. Here, we show by GFP-tagging that PbLAP4, PbLAP5 and PbLAP6, like their family members, are associated with the crystalloids.

Conformational co-dependence between Plasmodium berghei LCCL proteins promotes complex formation and stability.

Malaria parasites express a conserved family of LCCL-lectin adhesive-like domain proteins (LAPs) that have essential functions in sporozoite transmission. In Plasmodium falciparum all six family members are expressed in gametocytes and form a multi-protein complex. Intriguingly, knockout of P.

Malaria crystalloids: specialized structures for parasite transmission?

Malaria parasites possess many unique subcellular structures and organelles that are essential for the successful completion of the complex life cycle of Plasmodium in the vertebrate host and mosquito vector. Among these are the crystalloids: transient structures whose presence is restricted to the mosquito-specific ookinete and young oocyst stages of the parasite. Nearly five decades after they were first described, the crystalloids are back in the spotlight, with recent discoveries pointing to an important role in protein trafficking and sporozoite transmission that could be exploited as new targets for control of malaria transmission.

Malaria IMC1 membrane skeleton proteins operate autonomously and participate in motility independently of cell shape.

Plasmodium IMC1 (inner membrane complex 1) proteins comprise components of the subpellicular network, a lattice of intermediate filaments that form a structural part of the pellicle in the zoite stages of malaria parasites. Family members IMC1a and IMC1b are differentially expressed in sporozoites and ookinetes, respectively, but have functionally equivalent roles affecting cell morphology, strength, motility, and infectivity. Because of the coincident effects of previous imc1 gene disruptions on both zoite shape and locomotion, it has been impossible to ascribe a direct involvement in motility to these proteins.

Plasmodium berghei crystalloids contain multiple LCCL proteins.

Malaria crystalloids are unique organelles of unknown function that are present only in the mosquito-specific ookinete and early oocyst stages of the parasite. Recently, crystalloid formation in Plasmodium berghei was linked to the parasite protein PbSR, a member of the Plasmodium LCCL protein family composed of six modular multidomain proteins involved in sporozoite development and infectivity. Here, we show by fluorescent protein tagging that two other LCCL protein family members are targeted to the crystalloids in a similar way to PbSR.

IMC1b is a putative membrane skeleton protein involved in cell shape, mechanical strength, motility, and infectivity of malaria ookinetes.

Membrane skeletons are cytoskeletal elements that have important roles in cell development, shape, and structural integrity. Malaria parasites encode a conserved family of putative membrane skeleton proteins related to articulins. One member, IMC1a, is expressed in sporozoites and localizes to the pellicle, a unique membrane complex believed to form a scaffold onto which the ligands and glideosome are arranged to mediate parasite motility and invasion.

hOGG1(326), XRCC1(399) and XRCC3(241) polymorphisms influence micronucleus frequencies in human lymphocytes in vivo.

A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1(326), XRCC1(399) and XRCC3(241) gene polymorphisms on micronuclei (MN) frequency in human peripheral blood lymphocytes, as measured by the ex vivo/in vitro cytokinesis-block micronucleus (CBMN) assay. Each study addressed a type of occupational exposure potentially able to induce DNA strand breakage (styrene, ionising radiation, cobalt/hard metal, welding fumes and inorganic arsenite compounds), and therefore MN, as a result of base excision repair and double-strand break repair deficiencies. The effect of genotype, age, exposure to genotoxic agents and smoking habit on MN induction was determined using Poisson regression analysis in 171 occupationally exposed male workers and in 132 non-exposed male referents.