Unveiling a novel function of CD9 in surface compartmentalization of oocytes

Inoue, Naokazu; Saitô, Takako; Wada, Ikuo

doi:10.1242/dev.189985

Cited by 23 publications

(23 citation statements)

References 39 publications

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“…The disruption of F-actin significantly increased Juno/CD9 structures at regions proximal to maternal chromosomes, which suggests that F-actin is partially involved in the spatial control of Juno/CD9 structures. Furthermore, recently it was reported that CD9 functions to exclude Juno from the actin cap region ( Inoue et al, 2020 ). RanGTP may regulate the localization of Juno through CD9 protein.…”

Section: Discussionmentioning

confidence: 99%

RanGTP and the actin cytoskeleton keep paternal and maternal chromosomes apart during fertilization

Mori

Yao

Mishina

et al. 2021

Journal of Cell Biology

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Zygotes require two accurate sets of parental chromosomes, one each from the mother and the father, to undergo normal embryogenesis. However, upon egg–sperm fusion in vertebrates, the zygote has three sets of chromosomes, one from the sperm and two from the egg. The zygote therefore eliminates one set of maternal chromosomes (but not the paternal chromosomes) into the polar body through meiosis, but how the paternal chromosomes are protected from maternal meiosis has been unclear. Here we report that RanGTP and F-actin dynamics prevent egg–sperm fusion in proximity to maternal chromosomes. RanGTP prevents the localization of Juno and CD9, egg membrane proteins that mediate sperm fusion, at the cell surface in proximity to maternal chromosomes. Following egg–sperm fusion, F-actin keeps paternal chromosomes away from maternal chromosomes. Disruption of these mechanisms causes the elimination of paternal chromosomes during maternal meiosis. This study reveals a novel critical mechanism that prevents aneuploidy in zygotes.

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Section: Discussionmentioning

confidence: 99%

RanGTP and the actin cytoskeleton keep paternal and maternal chromosomes apart during fertilization

Mori

Yao

Mishina

et al. 2021

Journal of Cell Biology

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“…Similarly, At HAP2/GCS1 localization to the plasma membrane increases upon interaction with EC1 (Egg Cell 1), a small cysteine-rich protein secreted by the female gamete, which is necessary for sperm cell plasma membrane to gain fusion competence ( Sprunck et al, 2012 ). In mammals, the egg tetraspanin CD9 is proposed to be responsible for membrane organization and correct localization of adhesion- and fusion-related proteins, such as Juno ( Inoue et al, 2020 ; Umeda et al, 2020 ). In the mammalian sperm, Izumo1 localizes into the acrosome, giant intracellular vesicle in the head.…”

Section: Fine-tuning Of Gamete Fusionmentioning

confidence: 99%

Fusexins, HAP2/GCS1 and Evolution of Gamete Fusion

Brukman

Podbilewicz

2022

Front. Cell Dev. Biol.

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Gamete fusion is the climax of fertilization in all sexually reproductive organisms, from unicellular fungi to humans. Similarly to other cell-cell fusion events, gamete fusion is mediated by specialized proteins, named fusogens, that overcome the energetic barriers during this process. In recent years, HAPLESS 2/GENERATIVE CELL-SPECIFIC 1 (HAP2/GCS1) was identified as the fusogen mediating sperm-egg fusion in flowering plants and protists, being both essential and sufficient for the membrane merger in some species. The identification of HAP2/GCS1 in invertebrates, opens the possibility that a similar fusogen may be used in vertebrate fertilization. HAP2/GCS1 proteins share a similar structure with two distinct families of exoplasmic fusogens: the somatic Fusion Family (FF) proteins discovered in nematodes, and class II viral glycoproteins (e.g., rubella and dengue viruses). Altogether, these fusogens form the Fusexin superfamily. While some attributes are shared among fusexins, for example the overall structure and the possibility of assembly into trimers, some other characteristics seem to be specific, such as the presence or not of hydrophobic loops or helices at the distal tip of the protein. Intriguingly, HAP2/GCS1 or other fusexins have neither been identified in vertebrates nor in fungi, raising the question of whether these genes were lost during evolution and were replaced by other fusion machinery or a significant divergence makes their identification difficult. Here, we discuss the biology of HAP2/GCS1, its involvement in gamete fusion and the structural, mechanistic and evolutionary relationships with other fusexins.

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“…At the molecular level, Inoue and colleagues suggested that CD9 is crucial for the surface compartmentalization of GPI-anchored proteins, such as the sperm Izumo1 receptor JUNO, favoring gamete membrane fusion. 78 Crystal structure studies of CD9 have revealed that the LEL region of CD9 is critically involved in sperm-egg fusion. 59 All in all, these few examples illustrate the wide range of physiological functions mediated by the various interactions of CD9 and its membrane partners.…”

Section: Cd9 In Tetraspanin Web and Plasma Membranementioning

confidence: 99%

CD9, a tetraspanin target for cancer therapy?

Lorico

Lorico-Rappa

Karbanová

et al. 2021

Exp Biol Med (Maywood)

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In the present minireview, we intend to provide a brief history of the field of CD9 involvement in oncogenesis and in the metastatic process of cancer, considering its potential value as a tumor-associated antigenic target. Over the years, CD9 has been identified as a favorable prognostic marker or predictor of metastatic potential depending on the cancer type. To understand its implications in cancer beside its use as an antigenic biomarker, it is essential to know its physiological functions, including its molecular partners in a given cell system. Moreover, the discovery that CD9 is one of the most specific and broadly expressed markers of extracellular membrane vesicles, nanometer-sized entities that are released into extracellular space and various physiological body fluids and play a role in intercellular communication under physiological and pathological conditions, notably the establishment of cancer metastases, has added a new dimension to our knowledge of CD9 function in cancer. Here, we will discuss these issues as well as the possible cancer therapeutic implications of CD9, their limitations, and pitfalls.

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Unveiling a novel function of CD9 in surface compartmentalization of oocytes

Cited by 23 publications

References 39 publications

RanGTP and the actin cytoskeleton keep paternal and maternal chromosomes apart during fertilization

RanGTP and the actin cytoskeleton keep paternal and maternal chromosomes apart during fertilization

Fusexins, HAP2/GCS1 and Evolution of Gamete Fusion

CD9, a tetraspanin target for cancer therapy?

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