Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma

Bullen et al., 2016, Cell Host & Microbe 19, 349–360

Speaker: Chung-Ching Kuo (郭重慶)                  Time: 15:10~16:00, Oct. 12, 2016

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

Abstract:

Active host cell entry is an essential step in the propagation of obligate intracellular parasitism by apicomplexan parasite (Plasmodium spp. and Toxoplasma gondii). Invasive phase underpinned by timely and spatially controlled secretion of apical organelles termed microneme (1). Despite its central role in infectivity, current understanding of the molecular mechanisms governing microneme secretion is sparse. Microneme exocytosis is known to follow changes in extracellular potassium levels, implicates cyclic GMP-dependent protein kinase G (PKG) and phosphoinositide regulation and responds to an increase in intracellular calcium concentration., With a view to better deciphering microneme exocytosis, authors have focused here on diacylglycerol (DAG) and phosphatidic acid (PA), downstream products of phosphoinositide-phospholipase C (PI-PLC) signaling at the parasite plasma membrane (PPM). PI-PLC is the downstream mediator of PKG activity (2). PI-PLC acts on PI(4,5)P2 to generate the second messengers IP3 and DAG and stimulates Ca2+ release from the endoplasmic reticulum (ER) or other internal stores through unidentified receptors (3). Authors real that this balance is governed by the apicomplexan-specific DAG-kinase-1. In this article, the results show that a delicate balance between DAG and its downstream product, phosphatidic acid (PA), also identify an acylated pleckstrin-homology (PH) domain-containing protein (APH) on the microneme surface that senses PA during microneme secretion. All of these are essential for controlling microneme release.

References：

1.         Pushkar Sharma and Chetan E Chitnis (2013). Key molecular events during host cell invasion by Apicomplexan pathogens. Current Opinion in Microbiology 2013, 16:432–437

2.         Brochet M, Collins MO, Smith TK, Thompson E, Sebastian S, et al. Phosphoinositide Metabolism Links cGMP-Dependent Protein Kinase G to Essential Ca2+ Signals at Key Decision Points in the Life Cycle of Malaria Parasites. March 2014 | Volume 12 | Issue 3 | e1001806

3.         Alexandre Budua, b, Célia R.S. Garcia(2012). Generation of second messengers in Plasmodium. Volume 14, Issue 10, August 2012, Pages 787–795