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:

        頂复動物亞門多為能侵犯多種動物種戲的單細胞寄生原蟲，其invasion的方式多被保有相似的模式。例如透過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 和and rhoptry 的向外分泌，使寄生蟲能順利與host cell attach^[1].。 寄生蟲細胞中的鈣離子對於上述的apical organelles 的exocytosis 扮演重要的Cellular calcium acts as a key second messenger to regulate these apical organelles exocytosis 的角色^[2]。在此篇研究中，作者發現了一個與頂复門寄生蟲的invasion有重大關係的鈣離子調控. In this study, the authors have identified the specific role for the parasite homolog of calcineurin, a calcium-regulated phosphatase complex：calcineurin。, in host cell invasion by apicomplexans: calcineurin能幫助在宿主細胞外的寄生蟲更有效地attach在host cell上，作者使用 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限制calcineurin的表現來加以證明惡性瘧原蟲 combined the conditional expression of calcineurin to prove that the P. P. falciparum 的calcineurin complex是一個 is a specific regulator來調控其 of erythrocyte invasion by merozoite型態對紅血球的invasion。.同時作者發現 In addition, the calcineurin complex甚至能調控 functions independently of microneme exocytosis。在作者實驗中，. The calcineurin depletion 蟲株在與Cytochalasin D (CytD)藥物的作用下會無法有效率地attach紅血球，通過此實驗能看出cacineurin主要是影響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 momolecules mediating cellular adhesion, not ensuing host cell entry.，而非在於寄生蟲對宿主細胞的侵入作用。 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. 作者在同屬於頂复動物亞門的弓漿蟲 (Toxoplasma gondii) 的calcineurin也看到具有相同的功能性，The author proved the functional conservation of calcineurin in host cell attachment by Toxoplasma gondii, 因此合理推斷calcineurin對於Apicomplexans來說是在於分化前就存在的古老機制，使其在頂复動物亞門的多種品系中仍保有其功能性。

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).