Role of Hsp27 in Plasmodium berghei ookinetes

• Grant number: 16/05065-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2016
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Georgina Nuri Montagna
• Grantee: Karina Francine Bravo Caruso
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 13/14361-5 - Plasmodium parasite motility: identification of new candidates for drug targeting and validation of vaccine candidates, AP.JP

Abstract

Effective transmission blocking strategies to substantially reduce Plasmodium prevalence in mosquito populations are considered crucial for efforts to eliminate malaria. The efficiency of infection of the mosquito midgut is critical for malarial parasites to succeed in vector transmission. When mosquitoes feed on an infected host, sexual stages of malarial parasites are ingested in the mosquito midgut. In the blood bolus, they develop into motile ookinetes, which migrate towards the midgut epithelium. On the way, the ookinetes traverse the midgut peritrophic membrane matrix, invade the epithelial cells and migrate towards the basal lamina to form oocysts, within which numerous sporozoites develop. Although the molecular details of cell motility in the ookinete, are still largely unknown, active ookinete gliding has been shown to be dependent on dynamic actin and myosin and involve signalling pathways dependent on calcium , guanosine cyclic monophosphate (cGMP), guanylate cyclase and phosphatase. In previous studies, we found that a small heat shock protein, HSP20, is exclusively expressed in sporozoites and ookinetes. This chaperone can modulate speed and directionality of sporozoites prejudicing malaria natural transmission. Ookinetes formed in the blood bolus inside the mosquito midgut move substantially slower in the absence of Hsp20. Intriguingly, this deficiency did not impair establishment of infection and overall parasite population development inside the mosquito. Recently, we identified another small chaperone of 27 kDa (Hsp27) that appears exclusively expressed in ookinetes of P. berghei. Published proteome data support this observation. In general, Hsp27 is highly expressed in many cell types, where it has been identified as a potent regulator of the cytoskeleton as a result of its ability to inhibit actin polymerization. This property is dependent on the phosphorylation state of Hsp27, its structural organization, and the activation of diverse signaling mechanisms. We propose to analyze the molecular and cellular functions of Hsp27 in P.berghei ookinetes.