The genetic Ca2+ sensor GCaMP3 reveals multiple Ca2+ stores differentially coupled to Ca2+ entry in the human malaria parasite Plasmodium falciparum

Autor(es)

Borges-Pereira, Lucas ^{[1, 2]} ; Thomas, Samantha J. ^[2] ; dos Anjos e Silva, Amanda Laizy ^[3] ; Bartlett, Paula J. ^[2] ; Thomas, Andrew P. ^[2] ; Garcia, Celia R. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

^[2] Rutgers State Univ, New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ - USA

^[3] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Biological Chemistry; v. 295, n. 44, p. 14998-15012, OCT 30 2020.
• Citações Web of Science: 1

Resumo

Cytosolic Ca2+ regulates multiple steps in the host-cell invasion, growth, proliferation, and egress of blood-stage Plasmodium falciparum, yet our understanding of Ca2+ signaling in this endemic malaria parasite is incomplete. By using a newly generated transgenic line of P. falciparum (PfGCaMP3) that expresses constitutively the genetically encoded Ca2+ indicator GCaMP3, we have investigated the dynamics of Ca2+ release and influx elicited by inhibitors of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pumps, cyclopiazonic acid (CPA), and thapsigargin (Thg). Here we show that in isolated trophozoite phase parasites: (i) both CPA and Thg release Ca2+ from intracellular stores in P. falciparum parasites; (ii) Thg is able to induce Ca2+ release from an intracellular compartment insensitive to CPA; (iii) only Thg is able to activate Ca2+ influx from extracellular media, through a mechanism resembling store-operated Ca2+ entry, typical of mammalian cells; and (iv) the Thg-sensitive Ca2+ pool is unaffected by collapsing the mitochondria membrane potential with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone or the release of acidic Ca2+ stores with nigericin. These data suggest the presence of two Ca2+ pools in P. falciparum with differential sensitivity to the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pump inhibitors, and only the release of the Thg-sensitive Ca2+ store induces Ca2+ influx. Activation of the store-operated Ca2+ entry-like Ca2+ influx may be relevant for controlling processes such as parasite invasion, egress, and development mediated by kinases, phosphatases, and proteases that rely on Ca2+ levels for their activation. (AU)

• Processo FAPESP: 18/07177-7 - EMU concedido no processo 2011/51295-5: image system
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 16/13590-9 - MANUTENÇÃO DE LABORATÓRIO DE BIOLOGIA CELULAR E MOLECULAR DE Plasmodium falciparum: MANUTENÇÃO DE CEPAS DE Plasmodium E ORGANIZAÇÃO DO LABORATÓRIO
• Beneficiário: Amanda Laizy do Anjos e Silva
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 16/14411-0 - PfGCaMP3 como uma nova ferramenta para estudar a sinalização de Ca2+ no parasita da Malária humana Plasmodium falciparum
• Beneficiário: Lucas Borges Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/08684-7 - Decodificar aspectos da biologia celular e molecular do Plasmodium como uma ferramenta para desenvolver novos antimaláricos
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático