The Fer tyrosine kinase protects sperm from spontaneous acrosome reaction

Grinshtain, Elina; Shpungin, Sally; Baum, Micha; Nir, Uri; Breitbart, Haim

doi:10.1016/j.ydbio.2022.04.006

Cited by 3 publications

(12 citation statements)

References 63 publications

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“…The mitochondrial deformation caused by E260 suggests the involvement of Fer/FerT in maintaining key mitochondrial integrity sustaining processes in malignant cells. In compliance with these observations, treatment of sperm cells with the selective Fer/FerT inhibitor, E260, significantly impaired their motility, an effect that could be partially reversed by exposing the treated sperm cells to a high glucose concentration [ 26 ]. This suggests that E260 inhibits sperm motility through inhibition of the mitochondrial oxidative phosphorylation (Oxphos.)…”

Section: Fer and Fert: Newly Established Links Between Sperm And Canc...mentioning

confidence: 99%

“…As we noted above, inhibition of the Fer/FerT activity with the selective inhibitor, E260, downregulated the mitochondrial activity in both sperm and malignant cells. While this caused motility arrest in sperm [ 26 ], in cancer cells it evoked autophagy driven necrotic death [ 25 ]. This resulted from simultaneous alteration of parallel pathways following the inhibition of Fer/FerT in malignant cells.…”

Section: Fer and Fert: Newly Established Links Between Sperm And Canc...mentioning

confidence: 99%

“…This observation supports our notion regarding the regulation of the mitochondrial comp. I by Fer, in which its inhibition promotes sAR [ 26 ]. The precise regulation of the mitochondrial electron transport chain controls the production of ROS and protects the sperm from sAR.…”

Section: Roles Of Fer In Modulating Sperm Functionsmentioning

confidence: 99%

“…In our recent study, we show that inhibition of Fer inhibits actin polymerization during sperm capacitation resulting in the occurrence of sAR [ 26 ]. Actin polymerization during capacitation is essential for the development of hyperactivated motility [ 57 ] which is a known capacitation marker.…”

Section: Roles Of Fer In Modulating Sperm Functionsmentioning

confidence: 99%

“…Thus, we concluded that the regulatory, actin-polymerization-promoting activity of Fer supports proper sperm capacitation by protecting sperm from sAR. Interestingly, one of the ways through which Fer promotes actin polymerization in sperm is by restraining the activity of the phosphatase PP1, thereby maintaining the activation state of p-CAMKII [ 26 ]. We found that this ability of Fer to restrain the activity of PPI is exploited by cancer cells in their attempt to deregulate their cell cycle progression.…”

Section: Roles Of Fer In Modulating Sperm Functionsmentioning

confidence: 99%

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Fer and FerT: A New Regulatory Link between Sperm and Cancer Cells

Nir

Grinshtain

Breitbart

2023

IJMS

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Fer and its sperm and cancer specific variant, FerT, are non-receptor tyrosine kinases which play roles in cancer progression and metastasis. Recent studies have shed light on the regulatory role of these kinases in ensuring proper sperm function. Comparison of the regulatory cascades in which Fer and FerT are engaged in sperm and cancer cells presents an interesting picture, in which similar regulatory interactions of these enzymes are integrated in a similar or different regulatory context in the two cell types. These diverse compositions extend from the involvement of Fer in modulation of actin cytoskeleton integrity and function, to the unique regulatory interactions of Fer with PARP-1 and the PP1 phosphatase. Furthermore, recent findings link the metabolic regulatory roles of Fer and FerT in sperm and cancer cells. In the current review, we discuss the above detailed aspects, which portray Fer and FerT as new regulatory links between sperm and malignant cells. This perspective view can endow us with new analytical and research tools that will deepen our understanding of the regulatory trajectories and networks that govern these two multi-layered systems.

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Section: Fer and Fert: Newly Established Links Between Sperm And Canc...mentioning

confidence: 99%

Section: Fer and Fert: Newly Established Links Between Sperm And Canc...mentioning

confidence: 99%

Section: Roles Of Fer In Modulating Sperm Functionsmentioning

confidence: 99%

Section: Roles Of Fer In Modulating Sperm Functionsmentioning

confidence: 99%

Section: Roles Of Fer In Modulating Sperm Functionsmentioning

confidence: 99%

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Fer and FerT: A New Regulatory Link between Sperm and Cancer Cells

Nir

Grinshtain

Breitbart

2023

IJMS

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Functions and gene expression alterations of phospholipase C in gametes

Yeste,

Delgado-Bermúdez,

Jones

et al. 2023

Phospholipases in Physiology and Pathology

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Mechanisms That Protect Mammalian Sperm from the Spontaneous Acrosome Reaction

Breitbart,

Grinshtein

2023

IJMS

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To acquire the capacity to fertilize the oocyte, mammalian spermatozoa must undergo a series of biochemical reactions in the female reproductive tract, which are collectively called capacitation. The capacitated spermatozoa subsequently interact with the oocyte zona-pellucida and undergo the acrosome reaction, which enables the penetration of the oocyte and subsequent fertilization. However, the spontaneous acrosome reaction (sAR) can occur prematurely in the sperm before reaching the oocyte cumulus oophorus, thereby jeopardizing fertilization. One of the main processes in capacitation involves actin polymerization, and the resulting F-actin is subsequently dispersed prior to the acrosome reaction. Several biochemical reactions that occur during sperm capacitation, including actin polymerization, protect sperm from sAR. In the present review, we describe the protective mechanisms that regulate sperm capacitation and prevent sAR.

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The Fer tyrosine kinase protects sperm from spontaneous acrosome reaction

Cited by 3 publications

References 63 publications

Fer and FerT: A New Regulatory Link between Sperm and Cancer Cells

Fer and FerT: A New Regulatory Link between Sperm and Cancer Cells

Functions and gene expression alterations of phospholipase C in gametes

Mechanisms That Protect Mammalian Sperm from the Spontaneous Acrosome Reaction

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