期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1868, 期 4, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2021.118947
关键词
Acidocalcisome; Calcium; Inositol phosphates; IP3 receptor; Mitochondria; Polyphosphate
资金
- U.S. National Institutes of Health [AI140421, AI108222]
- Barbara and Sanford Orkin Eminent Scholar Endowment Fund
Trypanosoma cruzi and the T. brucei group of parasites are neglected diseases affecting millions of people globally. These microorganisms have complex life cycles involving insect vectors and mammalian hosts, and possess unique signaling pathways and receptor adaptations that differentiate them from their mammalian counterparts.
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 (polyP(3)), 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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