The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization

Herberg, Sarah; Gert, Krista R; Schleiffer, Alexander; Pauli, Andrea

doi:10.1126/science.aat7113

Cited by 91 publications

(187 citation statements)

References 57 publications

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“…However, unlike the high throughput techniques that enabled their discovery, functional de-orphanization of SEPs remains a resource-intensive endeavor that relies on fundamental approaches in experimental biology. To date, SEPs have been implicated in diverse functions ranging from cardiovascular and placental development, mTORC1 activation, calcium signaling, mRNA de-capping to membrane fusion, and oocyte fertilization [9][10][11][12][13][14][15] . However, whether SEPs have programmatic functions enabled by their small size remains an open question.…”

mentioning

confidence: 99%

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

et al. 2020

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The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution. Here, we show that the mitochondrial proteome, particularly the respiratory chain, is enriched for small proteins. Using a prediction and validation pipeline for SEPs, we report the discovery of 16 endogenous nuclear encoded, mitochondrial-localized SEPs (mito-SEPs). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN, a 71 a.a. peptide encoded by C12orf73, is essential for respiratory chain complex III (CIII) assembly. In human cells, BRAWNIN is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In zebrafish, Brawnin deletion causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BRAWNIN is essential for vertebrate oxidative phosphorylation. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism.

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confidence: 99%

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

et al. 2020

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“…A different but related protein, SPACA4, represents a very interesting case from an evolutionary perspective, and a possible gamete fusogen SPACA4/sperm acrosomal membrane protein 14 (SAMP14) is a Glycosylphosphatidylinositol (GPI)-anchored protein displayed on the surface of acrosome-reacted sperm whose role in mammals has to be fully elucidated [59]. An antibody raised against the recombinant SPACA4 blocked the fertilisation of ZP-free hamster eggs by human sperm [60], but as we discussed above, the generation of genetically modified mice will be necessary to determine whether this is an essential protein.…”

Section: Gamete Fusogens: An Evolutionary Perspectivementioning

confidence: 99%

“…An antibody raised against the recombinant SPACA4 blocked the fertilisation of ZP-free hamster eggs by human sperm [60], but as we discussed above, the generation of genetically modified mice will be necessary to determine whether this is an essential protein. Notably, the orthologue of SPACA4 in zebrafish-a protein named Bouncer-is essential for sperm-egg recognition in this model vertebrate [59]. In zebrafish, Bouncer is displayed on the surface of eggs and ensures species-specific fertilisation, a biology that has more relevance for broadcast-spawning species than in internally fertilising mammals.…”

Section: Gamete Fusogens: An Evolutionary Perspectivementioning

confidence: 99%

Find and fuse: Unsolved mysteries in sperm–egg recognition

Bianchi

Wright

2020

PLoS Biol

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Sexual reproduction is such a successful way of creating progeny with subtle genetic variations that the vast majority of eukaryotic species use it. In mammals, it involves the formation of highly specialised cells: the sperm in males and the egg in females, each carrying the genetic inheritance of an individual. The interaction of sperm and egg culminates with the fusion of their cell membranes, triggering the molecular events that result in the formation of a new genetically distinct organism. Although we have a good cellular description of fertilisation in mammals, many of the molecules involved remain unknown, and especially the identity and role of cell surface proteins that are responsible for sperm–egg recognition, binding, and fusion. Here, we will highlight and discuss these gaps in our knowledge and how the role of some recently discovered sperm cell surface and secreted proteins contribute to our understanding of this fundamental process.

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“…Recently, another novel gene from zebrafish was cloned. The gene termed "Bouncer" showed the closest homology to the EPG and was also found to be Ly6/uPAR protein and is a crucial fertilization factor in the zebrafish 33 . Nevertheless, very little is known about the EPG function in its natural environment or when expressed in mammalian cells.…”

Section: Trajectory Analysis Algorithm Show Notably Different Epg Promentioning

confidence: 99%

Functional Characterization of an Electromagnetic Perceptive Protein

Mitra

Barnaba

Schmidt

et al. 2020

Preprint

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Magnetoreception, the response to geomagnetic fields is a well described phenomenon in nature. However, it is likely that convergent evolution led to different mechanisms in different organisms. One intriguing example is the unique Electromagnetic Perceptive Gene (EPG) from the glass catfish Kryptopterus vitreolus, that can remotely control cellular function, upon magnetic stimulation in in-vitro and in animal models. Here, we report for the first time the cellular location and orientation of the EPG protein. We utilized a differential labelling technique in determining that the EPG protein is a membrane anchored protein with an N-terminal extracellular domain. The kinetics and diffusion dynamics of the EPG protein in response to magnetic stimulation was also elucidated using single particle imaging and tracking. Pulse chase labelling and Total Internal Reflection Fluorescence (TIRF) imaging revealed an increase in EPG kinetics post magnetic stimulation activation at a single particle level. Trajectory analysis show notably different EPG protein kinetics before and after magnetic stimulation in both 2 (free vs bound particle) and 3 state (free vs intermediate vs bound particle) tracking models. These data serve to provide additional information that support and understand the underlying biophysical mechanisms behind EPG activation by magnetic stimulation. In conclusion, our results provide evidence for the basis of magnetoreception in EPG protein that would aid in future studies that seek to understand this novel mechanism. This study is important for understanding the phenomenon of magnetoreception as well as developing new technologies for magnetogenetics – the utilization of electromagnetic fields to remotely control cellular function.Graphical TOCElucidation of magnetoreception in a fish derived Electromagnetic Perceptive Gene (EPG), using genetic tagging and single particle tracking with Total Internal Reflection Fluorescence (TIRF) suggests changes in kinetics of membranal motion upon stimulation by magnetic field.

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The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization

Cited by 91 publications

References 57 publications

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

Find and fuse: Unsolved mysteries in sperm–egg recognition

Functional Characterization of an Electromagnetic Perceptive Protein

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