原生動物“剛地弓線蟲”（人體中的一種機會主義病原體）分泌被稱為“微絲”的細胞器，它們在寄生蟲運動性,、宿主-細胞入侵和退出中扮演一個關(guān)鍵角色,。
現(xiàn)在，這個過程被發(fā)現(xiàn)涉及“剛地弓線蟲”依賴于鈣的蛋白激酶-1(TgCDPK1),。哺乳動物宿主中這個激酶家族的缺乏使得這一蛋白成為藥物設計的一個有吸引力的目標,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09022
Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma
Sebastian Lourido1, Joel Shuman1, Chao Zhang2, Kevan M. Shokat2, Raymond Hui3 & L. David Sibley1
Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA
Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, California 94158, USA
Structural Genomics Consortium, University Toronto, MaRS South Tower, Suite 732, 101 College Street, Toronto, Canada M5G 1L7
Calcium-regulated exocytosis is a ubiquitous process in eukaryotes, whereby secretory vesicles fuse with the plasma membrane and release their contents in response to an intracellular calcium surge1. This process regulates various cellular functions such as plasma membrane repair in plants and animals2, 3, the discharge of defensive spikes in Paramecium4, and the secretion of insulin from pancreatic cells, immune modulators from lymphocytes, and chemical transmitters from neurons5. In animal cells, serine/threonine kinases including cAMP-dependent protein kinase, protein kinase C and calmodulin kinases have been implicated in calcium-signal transduction leading to regulated secretion1, 6, 7. Although plants and protozoa also regulate secretion by means of intracellular calcium, the method by which these signals are relayed has not been explained. Here we show that the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) is an essential regulator of calcium-dependent exocytosis in this opportunistic human pathogen. Conditional suppression of TgCDPK1 revealed that it controls calcium-dependent secretion of specialized organelles called micronemes, resulting in a block of essential phenotypes including parasite motility, host-cell invasion, and egress. These phenotypes were recapitulated by using a chemical biology approach in which pyrazolopyrimidine-derived compounds specifically inhibited TgCDPK1 and disrupted the parasite’s life cycle at stages dependent on microneme secretion. Inhibition was specific to TgCDPK1, because expression of a resistant mutant kinase reversed sensitivity to the inhibitor. TgCDPK1 is conserved among apicomplexans and belongs to a family of kinases shared with plants and ciliates8, suggesting that related CDPKs may have a function in calcium-regulated secretion in other organisms. Because this kinase family is absent from mammalian hosts, it represents a validated target that may be exploitable for chemotherapy against T.?gondii and related apicomplexans.
