The IP(3) receptor and Ca(2+) signaling in trypanosomes.
The IP(3) receptor and Ca(2+) signaling in trypanosomes.
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DOI：
10.1016/j.bbamcr.2021.118947
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Docampo R;Huang G
克氏锥虫和布鲁氏锥虫群引起被忽视的疾病，影响着全世界数百万人。这些单细胞微生物具有复杂的生命周期，涉及昆虫媒介和哺乳动物宿主。这两组病原体都具有肌醇1,4,5-三磷酸(IP3)/二酰基甘油（DAG）信号通路和IP3受体，但具有谱系特异性适应，使它们与哺乳动物的同类不同。将磷脂酰肌醇4,5-二磷酸（PIP2）水解为IP3的磷脂酶C （PLC）是n端肉豆蔻酰化和棕榈酰化的。酸钙体是一种富含多磷酸盐的溶酶体相关细胞器，是细胞内Ca2+的主要储存体。肌醇1,4,5-三磷酸受体（IP3R）定位于酸钙体而不是内质网。锥虫的IP3R受多磷酸（polyP）水解产物luminal phosphate和焦磷酸（pyrophosphate）的刺激，而受三聚磷酸（polyyp3）的抑制，三聚磷酸（polyyp3）是酸钙体中最丰富的polyP。Ca2+信号对于宿主细胞的侵袭和分化以及维持细胞的生物能量是重要的。
Trypanosoma cruzi, and the T. brucei group of parasites cause neglected diseases that affect millions of people around the world. These unicellular microorganisms have complex life cycles involving an insect vector and a mammalian host. Both groups of pathogens possess an inositol 1,4,5-trisphosphate (IP3)/diacylglycerol (DAG) signaling pathway, and an IP3 receptor, but with lineage-specific adaptations that make them different from their mammalian counterparts. The phospholipase C (PLC), which hydrolyzes phosphatidyl inositol 4,5-bisphosphate (PIP2) to IP3 is N-terminally myristoylated and palmitoylated. Acidocalcisomes, which are lysosome-related organelles rich in polyphosphate, are the main intracellular Ca2+ stores. The inositol 1,4,5-trisphosphate receptor (IP3R) localizes to acidocalcisomes instead of the endoplasmic reticulum. The trypanosome IP3R is stimulated by luminal phosphate and pyrophosphate, which are hydrolysis products of polyphosphate (polyP), and inhibited by tripolyphosphate (polyP3), which is the most abundant polyP in acidocalcisomes. Ca2+ signaling is important for host cell invasion and differentiation and to maintain cellular bioenergetics.
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