Parasite Calcineurin Regulates Host Cell Recognition and Attachment by Apicomplexans

Aditya S. Paul, Sudeshna Saha, Klemens Engelberg,Tim W. Gilberger, Marc-Jan Gubbels,           Manoj T. Duraisingh

Cell host & microbe 18.1 (2015): 49-60

Speaker: Jia-Yian Wu (武珈言)                                      Time: 14:10~15:00, Oct. 7^th, 2015.

Commentator: Dr. Jyh-Wei Shin (辛致煒 老師)            Place: Room 601

Abstract:

        Apicomplexans attach to and invade cells in various animal species, yet they share a conserved mode of invasion, which involves a sequential secretion of these apical organelles, microneme and rhoptry ^[1]. Cellular calcium acts as a key second messenger to regulate these apical organelles exocytosis ^[2]. In this study, the authors have identified the specific role for the parasite homolog of calcineurin, a calcium-regulated phosphatase complex, in host cell invasion by apicomplexans: calcineurin is required for the extracellular parasite to strongly attach to the host before intracellular entry. In blood stage, the Plasmodium falciparum requires cellular calcium for passage of invasive merozoite forms between erythrocytes. The authors used the calcineurin inhibitors combined the conditional expression of calcineurin to prove that the P. falciparum calcineurin complex is a specific regulator of erythrocyte invasion by merozoite. In addition, the calcineurin complex functions independently of microneme exocytosis. The calcineurin depletion strongly reduces erythrocyte attachment by merozoites in the presence of cytochalasin D (CytD), a small molecule inhibitor of actin polymerization, suggests a close functional association with molecules mediating cellular adhesion, not ensuing host cell entry. The calcineurin depletion does not influence the sensitivity of parasites to CytD and thus erythrocyte entry following attachment, underscoring the specificity of calcineurin to host cell attachment. The author proved the functional conservation of calcineurin in host cell attachment by Toxoplasma gondii, demonstrating an ancestral mechanism for parasitism used by diverse Apicomplexans. The role for calcineurin in a specific form of attachment via host receptors shows a conserved link between species-specific mechanisms determining host cell tropism and a general mode of apicomplexan invasion applied to diverse host cells.

References:

[1].    Besteiro, S., Dubremetz, J. F., & Lebrun, M. (2011). The moving junction of apicomplexan parasites: a key structure for invasion. Cellular microbiology, 13(6), 797-805.

[2].    Singh, S., Alam, M. M., Pal-Bhowmick, I., Brzostowski, J. A., & Chitnis, C. E. (2010). Distinct external signals trigger sequential release of apical organelles during erythrocyte invasion by malaria parasites. PLoS pathogens, 6(2).