The zinc transporter ZIP9 (Slc39a9) regulates zinc dynamics essential to egg activation in zebrafish

Converse, Aubrey; Thomas, Peter

doi:10.1038/s41598-020-72515-4

Cited by 22 publications

(11 citation statements)

References 54 publications

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“…Our results identify SLC39A9 -encoded protein ZIP9 as a Golgi resident protein. ZIP9 is the only known zinc transporter to have a hormone receptor activity (53) and has been described to have an important role in regulating cytosolic zinc levels (54). While its Golgi-association data are limited, a previous report showed a colocalization between ZIP9 and TGN46, a trans -Golgi network marker (31).…”

Section: Discussionmentioning

confidence: 99%

Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content

Fasimoye

Dong

Nirujogi

et al. 2022

Preprint

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The Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signalling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease. Golgi dysfunction is associated with a broad spectrum of diseases including cancer, neurodegeneration, and cardiovascular diseases. To allow the study of the Golgi at high resolution, we report a rapid immunoprecipitation technique (Golgi-IP) to isolate intact Golgi mini-stacks for subsequent analysis of their content. By fusing the Golgi resident protein TMEM115 to three tandem HA epitopes (GolgiTAG), we purified the Golgi using Golgi-IP with minimal contamination from other compartments. We then established an analysis pipeline using liquid chromatography coupled with mass spectrometry to characterize the human Golgi proteome, metabolome and lipidome. Subcellular proteomics confirmed known Golgi proteins and identified novel ones. Metabolite profiling established the first known human Golgi metabolome and revealed the selective enrichment of uridine-diphosphate (UDP) sugars and their derivatives, which is consistent with their roles in protein and lipid glycosylation. Furthermore, targeted metabolomics validated SLC35A2 as the subcellular transporter for UDP-hexose. Finally, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylserine are the most abundant Golgi lipids and that glycosphingolipids are enriched in this compartment. Altogether, our work establishes a comprehensive molecular map of the human Golgi and provides a powerful method to study the Golgi with high precision in health and disease states.

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Section: Discussionmentioning

confidence: 99%

Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content

Fasimoye

Dong

Nirujogi

et al. 2022

Preprint

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“…Female zebrafish zip9 mutants exhibited reduced fecundity and egg viability compared with wild-type. Additionally, oocytes from zip9 mutants exhibited reduced diameter cortical vesicles and smaller zinc-containing vesicles compared to oocytes from wild-type fish ( 110 ). These results suggest that zinc influences egg activation, but they do not address whether intracellular zinc concentration or ZIP9 function in oocytes is androgen-dependent.…”

Section: Membrane Androgen Receptorsmentioning

confidence: 97%

The Interface of Nuclear and Membrane Steroid Signaling

Treviño

Gorelick

2021

Endocrinology

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Steroid hormones bind receptors in the cell nucleus and in the cell membrane. The most widely studied class of steroid hormone receptors are the nuclear receptors, named for their function as ligand-dependent transcription factors in the cell nucleus. Nuclear receptors, such as estrogen receptor alpha, can also be anchored to the plasma membrane, where they respond to steroids by activating signaling pathways independent of their function as transcription factors. Steroids can also bind integral membrane proteins, such as the G protein-coupled estrogen receptor. Membrane estrogen and progestin receptors have been cloned and characterized in vitro and influence the development and function of many organ systems. Membrane androgen receptors were cloned and characterized in vitro, but their function as androgen receptors in vivo is unresolved. We review the identity and function of membrane proteins that bind estrogens, progestins and androgens. We discuss evidence that membrane glucocorticoid and mineralocorticoid receptors exist, and whether glucocorticoid and mineralocorticoid nuclear receptors act at the cell membrane. In many cases, integral membrane steroid receptors act independently of nuclear steroid receptors, even though they may share a ligand.

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“…Similar observations have been made in human, bovine, porcine, and primate systems [ 197 , 198 ], suggesting (like Ca 2+ ) that this Zn 2+ spark is highly conserved (at least in mammals) [ 199 , 200 ]. Although recent studies do suggest that a similar process involving Zn 2+ depletion at fertilisation occurs in Drosophila [ 201 ] and zebrafish [ 202 ]. Immature mouse oocytes are unable to elicit a Zn 2+ spark, indicating Zn 2+ accumulation is required during meiotic maturation [ 203 , 204 ].…”

Section: The Role Of Zinc (Zn 2+ )mentioning

confidence: 99%

The Therapeutic and Diagnostic Potential of Phospholipase C Zeta, Oocyte Activation, and Calcium in Treating Human Infertility

et al. 2023

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Oocyte activation, a fundamental event during mammalian fertilisation, is initiated by concerted intracellular patterns of calcium (Ca2+) release, termed Ca2+ oscillations, predominantly driven by testis-specific phospholipase C zeta (PLCζ). Ca2+ exerts a pivotal role in not just regulating oocyte activation and driving fertilisation, but also in influencing the quality of embryogenesis. In humans, a failure of Ca2+ release, or defects in related mechanisms, have been reported to result in infertility. Furthermore, mutations in the PLCζ gene and abnormalities in sperm PLCζ protein and RNA, have been strongly associated with forms of male infertility where oocyte activation is deficient. Concurrently, specific patterns and profiles of PLCζ in human sperm have been linked to parameters of semen quality, suggesting the potential for PLCζ as a powerful target for both therapeutics and diagnostics of human fertility. However, further to PLCζ and given the strong role played by Ca2+ in fertilisation, targets down- and up-stream of this process may also present a significantly similar level of promise. Herein, we systematically summarise recent advancements and controversies in the field to update expanding clinical associations between Ca2+-release, PLCζ, oocyte activation and human fertility. We discuss how such associations may potentially underlie defective embryogenesis and recurrent implantation failure following fertility treatments, alongside potential diagnostic and therapeutic avenues presented by oocyte activation for the diagnosis and treatment of human infertility.

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The zinc transporter ZIP9 (Slc39a9) regulates zinc dynamics essential to egg activation in zebrafish

Cited by 22 publications

References 54 publications

Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content

Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content

The Interface of Nuclear and Membrane Steroid Signaling

The Therapeutic and Diagnostic Potential of Phospholipase C Zeta, Oocyte Activation, and Calcium in Treating Human Infertility

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