Intracellular Trafficking and Organelle Biogenesis in Apicomplexan Parasites

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Cell Biology and Tissue Engineering".

Deadline for manuscript submissions: closed (23 June 2021) | Viewed by 28021

Special Issue Editor


E-Mail Website
Guest Editor
Institute for Integrative Biology of the Cell (I2BC), CNRS-CEA, Université Paris-Saclay, 91190 Paris, France
Interests: intracellular transport; protein/lipid trafficking; secretory organelle biogenesis; host–toxoplasma interactions; host infection; parasite virulence

Special Issue Information

Dear Colleagues,

The phylum Apicomplexa comprises more than 5000 single-celled parasites of clinical and economic importance, including Plasmodium falciparum, the agents of malaria, and Toxoplasma gondii, the cause of toxoplasmosis. These obligate intracellular parasites possess a highly complex endomembrane system to build morphologically distinct organelles that are essential for invasion and hijacking multiple biological functions of the hosts. The accurate targeting of proteins and lipids to their final destination is a crucial process in all living cells and apicomplexan parasites as well. Due to the complexity of the internal organization of these parasites, a wide panoply of trafficking factors are required for the correct sorting of proteins and lipids towards their various organelles. However, these parasites contain only a core set of these trafficking factors. In addition, recent insight suggests trafficking of proteins and other materials into T. gondii and P. falciparum via unusual and novel pathways. These findings uncover evidence that apicomplexan parasites utilize both conventional and unconventional pathways to promote maturation and trafficking of proteins and lipids destined for the formation of these parasite-specific organelles. In this Special Issue, reviews will report on different trafficking machineries and mechanisms which are involved in the biogenesis of parasite-specific organelles.

Dr. Stanislas Tomavo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Apicomplexan parasites
  • Protein trafficking
  • Lipid trafficking
  • Endomembrane system
  • Endolysosomal pathway
  • Organelle biogenesis
  • Hijacking of host cell functions
  • Host–parasite interactions

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 2419 KiB  
Communication
Autophagy Pathways in the Genesis of Plasmodium-Derived Microvesicles: A Double-Edged Sword?
by Inès Leleu, Jeremy Alloo, Pierre-André Cazenave, Jacques Roland and Sylviane Pied
Life 2022, 12(3), 415; https://doi.org/10.3390/life12030415 - 12 Mar 2022
Cited by 2 | Viewed by 2449
Abstract
Malaria, caused by Plasmodium species (spp.), is a deadly parasitic disease that results in approximately 400,000 deaths per year globally. Autophagy pathways play a fundamental role in the developmental stages of the parasite within the mammalian host. They are also involved in the [...] Read more.
Malaria, caused by Plasmodium species (spp.), is a deadly parasitic disease that results in approximately 400,000 deaths per year globally. Autophagy pathways play a fundamental role in the developmental stages of the parasite within the mammalian host. They are also involved in the production of Plasmodium-derived extracellular vesicles (EVs), which play an important role in the infection process, either by providing nutrients for parasite growth or by contributing to the immunopathophysiology of the disease. For example, during the hepatic stage, Plasmodium-derived EVs contribute to parasite virulence by modulating the host immune response. EVs help in evading the different autophagy mechanisms deployed by the host for parasite clearance. During cerebral malaria, on the other hand, parasite-derived EVs promote an astrocyte-mediated inflammatory response, through the induction of a non-conventional host autophagy pathway. In this review, we will discuss the cross-talk between Plasmodium-derived microvesicles and autophagy, and how it influences the outcome of infection. Full article
Show Figures

Figure 1

22 pages, 21826 KiB  
Communication
Ferlins and TgDOC2 in Toxoplasma Microneme, Rhoptry and Dense Granule Secretion
by Daniel N. A. Tagoe, Allison A. Drozda, Julia A. Falco, Tyler J. Bechtel, Eranthie Weerapana and Marc-Jan Gubbels
Life 2021, 11(3), 217; https://doi.org/10.3390/life11030217 - 09 Mar 2021
Cited by 6 | Viewed by 3358
Abstract
The host cell invasion process of apicomplexan parasites like Toxoplasma gondii is facilitated by sequential exocytosis of the microneme, rhoptry and dense granule organelles. Exocytosis is facilitated by a double C2 domain (DOC2) protein family. This class of C2 domains is derived from [...] Read more.
The host cell invasion process of apicomplexan parasites like Toxoplasma gondii is facilitated by sequential exocytosis of the microneme, rhoptry and dense granule organelles. Exocytosis is facilitated by a double C2 domain (DOC2) protein family. This class of C2 domains is derived from an ancestral calcium (Ca2+) binding archetype, although this feature is optional in extant C2 domains. DOC2 domains provide combinatorial power to the C2 domain, which is further enhanced in ferlins that harbor 5–7 C2 domains. Ca2+ conditionally engages the C2 domain with lipids, membranes, and/or proteins to facilitating vesicular trafficking and membrane fusion. The widely conserved T. gondii ferlins 1 (FER1) and 2 (FER2) are responsible for microneme and rhoptry exocytosis, respectively, whereas an unconventional TgDOC2 is essential for microneme exocytosis. The general role of ferlins in endolysosmal pathways is consistent with the repurposed apicomplexan endosomal pathways in lineage specific secretory organelles. Ferlins can facilitate membrane fusion without SNAREs, again pertinent to the Apicomplexa. How temporal raises in Ca2+ combined with spatiotemporally available membrane lipids and post-translational modifications mesh to facilitate sequential exocytosis events is discussed. In addition, new data on cross-talk between secretion events together with the identification of a new microneme protein, MIC21, is presented. Full article
Show Figures

Figure 1

Review

Jump to: Research

20 pages, 1404 KiB  
Review
Secreted Effectors Modulating Immune Responses to Toxoplasma gondii
by Tadakimi Tomita, Rebekah B. Guevara, Lamisha M. Shah, Andrews Y. Afrifa and Louis M. Weiss
Life 2021, 11(9), 988; https://doi.org/10.3390/life11090988 - 20 Sep 2021
Cited by 16 | Viewed by 3355
Abstract
Toxoplasma gondii is an obligate intracellular parasite that chronically infects a third of humans. It can cause life-threatening encephalitis in immune-compromised individuals. Congenital infection also results in blindness and intellectual disabilities. In the intracellular milieu, parasites encounter various immunological effectors that have been [...] Read more.
Toxoplasma gondii is an obligate intracellular parasite that chronically infects a third of humans. It can cause life-threatening encephalitis in immune-compromised individuals. Congenital infection also results in blindness and intellectual disabilities. In the intracellular milieu, parasites encounter various immunological effectors that have been shaped to limit parasite infection. Parasites not only have to suppress these anti-parasitic inflammatory responses but also ensure the host organism’s survival until their subsequent transmission. Recent advancements in T. gondii research have revealed a plethora of parasite-secreted proteins that suppress as well as activate immune responses. This mini-review will comprehensively examine each secreted immunomodulatory effector based on the location of their actions. The first section is focused on secreted effectors that localize to the parasitophorous vacuole membrane, the interface between the parasites and the host cytoplasm. Murine hosts are equipped with potent IFNγ-induced immune-related GTPases, and various parasite effectors subvert these to prevent parasite elimination. The second section examines several cytoplasmic and ER effectors, including a recently described function for matrix antigen 1 (MAG1) as a secreted effector. The third section covers the repertoire of nuclear effectors that hijack transcription factors and epigenetic repressors that alter gene expression. The last section focuses on the translocation of dense-granule effectors and effectors in the setting of T. gondii tissue cysts (the bradyzoite parasitophorous vacuole). Full article
Show Figures

Figure 1

13 pages, 683 KiB  
Review
Protein Sorting in Plasmodium Falciparum
by D.C. Ghislaine Mayer
Life 2021, 11(9), 937; https://doi.org/10.3390/life11090937 - 09 Sep 2021
Viewed by 11459
Abstract
Plasmodium falciparum is a unicellular eukaryote with a very polarized secretory system composed of micronemes rhoptries and dense granules that are required for host cell invasion. P. falciparum, like its relative T. gondii, uses the endolysosomal system to produce the secretory [...] Read more.
Plasmodium falciparum is a unicellular eukaryote with a very polarized secretory system composed of micronemes rhoptries and dense granules that are required for host cell invasion. P. falciparum, like its relative T. gondii, uses the endolysosomal system to produce the secretory organelles and to ingest host cell proteins. The parasite also has an apicoplast, a secondary endosymbiotic organelle, which depends on vesicular trafficking for appropriate incorporation of nuclear-encoded proteins into the apicoplast. Recently, the central molecules responsible for sorting and trafficking in P. falciparum and T. gondii have been characterized. From these studies, it is now evident that P. falciparum has repurposed the molecules of the endosomal system to the secretory pathway. Additionally, the sorting and vesicular trafficking mechanism seem to be conserved among apicomplexans. This review described the most recent findings on the molecular mechanisms of protein sorting and vesicular trafficking in P. falciparum and revealed that P. falciparum has an amazing secretory machinery that has been cleverly modified to its intracellular lifestyle. Full article
Show Figures

Figure 1

16 pages, 1004 KiB  
Review
Do All Coccidia Follow the Same Trafficking Rules?
by Virginia Marugan-Hernandez, Gonzalo Sanchez-Arsuaga, Sue Vaughan, Alana Burrell and Fiona M. Tomley
Life 2021, 11(9), 909; https://doi.org/10.3390/life11090909 - 31 Aug 2021
Cited by 3 | Viewed by 2766
Abstract
The Coccidia are a subclass of the Apicomplexa and include several genera of protozoan parasites that cause important diseases in humans and animals, with Toxoplasma gondii becoming the ‘model organism’ for research into the coccidian molecular and cellular processes. The amenability to the [...] Read more.
The Coccidia are a subclass of the Apicomplexa and include several genera of protozoan parasites that cause important diseases in humans and animals, with Toxoplasma gondii becoming the ‘model organism’ for research into the coccidian molecular and cellular processes. The amenability to the cultivation of T. gondii tachyzoites and the wide availability of molecular tools for this parasite have revealed many mechanisms related to their cellular trafficking and roles of parasite secretory organelles, which are critical in parasite-host interaction. Nevertheless, the extrapolation of the T. gondii mechanisms described in tachyzoites to other coccidian parasites should be done carefully. In this review, we considered published data from Eimeria parasites, a coccidian genus comprising thousands of species whose infections have important consequences in livestock and poultry. These studies suggest that the Coccidia possess both shared and diversified mechanisms of protein trafficking and secretion potentially linked to their lifecycles. Whereas trafficking and secretion appear to be well conversed prior to and during host-cell invasion, important differences emerge once endogenous development commences. Therefore, further studies to validate the mechanisms described in T. gondii tachyzoites should be performed across a broader range of coccidians (including T. gondii sporozoites). In addition, further genus-specific research regarding important disease-causing Coccidia is needed to unveil the individual molecular mechanisms of pathogenesis related to their specific lifecycles and hosts. Full article
Show Figures

Figure 1

18 pages, 1091 KiB  
Review
Emerging Mechanisms of Endocytosis in Toxoplasma gondii
by Olivia L. McGovern, Yolanda Rivera-Cuevas and Vern B. Carruthers
Life 2021, 11(2), 84; https://doi.org/10.3390/life11020084 - 25 Jan 2021
Cited by 11 | Viewed by 3653
Abstract
Eukaryotes critically rely on endocytosis of autologous and heterologous material to maintain homeostasis and to proliferate. Although mechanisms of endocytosis have been extensively identified in mammalian and plant systems along with model systems including budding yeast, relatively little is known about endocytosis in [...] Read more.
Eukaryotes critically rely on endocytosis of autologous and heterologous material to maintain homeostasis and to proliferate. Although mechanisms of endocytosis have been extensively identified in mammalian and plant systems along with model systems including budding yeast, relatively little is known about endocytosis in protozoan parasites including those belonging to the phylum Apicomplexa. Whereas it has been long established that the apicomplexan agents of malaria (Plasmodium spp.) internalize and degrade hemoglobin from infected red blood cells to acquire amino acids for growth, that the related and pervasive parasite Toxoplasma gondii has a functional and active endocytic system was only recently discovered. Here we discuss emerging and hypothesized mechanisms of endocytosis in Toxoplasma gondii with reference to model systems and malaria parasites. Establishing a framework for potential mechanisms of endocytosis in Toxoplasma gondii will help guide future research aimed at defining the molecular basis and biological relevance of endocytosis in this tractable and versatile parasite. Full article
Show Figures

Figure 1

Back to TopTop