FAK regulates actin polymerization during sperm capacitation via the ERK2/GEF-H1/RhoA signaling pathway

Salgado‐Lucio, Monica L.; Ramírez‐Ramírez, Danelia; Jorge-Cruz, Coral Y.; Roa-Espitia, Ana Lilia; Hernández‐González, Enrique O.

doi:10.1242/jcs.239186

Cited by 12 publications

(10 citation statements)

References 90 publications

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“…Additionally, our recent publication showed that ex vivo manipulation of stress signaling in spermatozoa changed transcriptional profiles of 84% mitochondrial dynamics/functionality markers and that most of these effects are mediated through α1-and/or-β-adrenergic receptors [ 14 ], which are very well known activators of ADCY-cAMP-PRKA-signaling [ 15 ]. In relation to MAPK signaling, our results are showing increased transcription of 80% of MAPKs, and they could be compared with findings that testicular hyperthermia induces both MAPK1/3 and MAPK14 [ 68 ] and that MEK1/2 and ERK2 regulate actin polymerization associated with spermatozoa capacitation [ 69 ].…”

Section: Discussionsupporting

confidence: 58%

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Starovlah

Pletikosic

Kostic

et al. 2021

IJMS

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Here, we study possible mechanisms of (in/sub)fertility related to the acute or repeated psychological stresses (the most common stresses in human society) by following the transcriptional profile of 22 mitochondrial dynamics/function markers and 22 signaling molecules regulating both mitochondrial dynamics and spermatozoa number/functionality. An in vivo study mimicking acute (once for 3 h) and repeated (3 h for 10 consecutive days) psychophysical stress was performed on adult rats. The analysis of hormones, the number/functionality of spermatozoa, and 44 transcriptional markers were performed on individual samples from up to 12 animals per group. Results showed that both types of stress reduced spermatozoa functionality (acute by 4.4-fold, repeated by 3.3-fold) and ATP production (acute by 2.3-fold, repeated by 14.5-fold), while only repeated stress reduces the number of spermatozoa (1.9-fold). Stress significantly disturbed transcription of 34-out-of-44 markers (77%). Mitochondrial dynamics and functionality markers: 18-out-of-22 =>82% (mitochondrial-biogenesis-markers –>6-out-of-8 =>75%; mitochondrial-fusion-markers –>3-out-of-3 =>100%; mitochondrial-fission-markers –>1-out-of-2 =>50%; mitochondrial-autophagy-markers –>3-out-of-3 =>100%; mitochondrial-functionality-markers –>5-out-of-6 =>83%). Markers of signaling pathways regulating both mitochondrial dynamics/functionality and spermatozoa number/functionality important for male (in/sub)fertility –>16-out-of-22 =>73% (cAMP-signaling-markers –>8-out-of-12 =>67%; MAPK-signaling-markers –>8-out-of-10 =>80%). Accordingly, stress-triggered changes of transcriptional profile of mitochondrial dynamics/functionality markers as well as signaling molecules regulating both mitochondrial dynamics and spermatozoa number and functionality represent adaptive mechanisms.

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Section: Discussionsupporting

confidence: 58%

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Starovlah

Pletikosic

Kostic

et al. 2021

IJMS

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“…In the present work, we observed an increase in F-actin levels in capacitated cryopreserved bull sperm after 15 min capacitation, and a decrease in polymerized actin 30 min later. Similar actin polymerization dynamics displaying a peak has been described in other species such as guinea pig 55 .…”

Section: Discussionsupporting

confidence: 78%

Cyclic AMP efflux through MRP4 regulates actin dynamics signalling pathway and sperm motility in bovines

Chiarante

Alonso

Plaza³

et al. 2020

Sci Rep

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Previously we demonstrated that multidrug resistance-associated protein 4 transporter (MRP4) mediates cAMP efflux in bovine spermatozoa and that extracellular cAMP (ecAMP) triggers events associated to capacitation. Here, we deepen the study of the role of MRP4 in bovine sperm function by using MK571, an MRP4 inhibitor. The incubation of spermatozoa with MK571 during 45 min inhibited capacitation-associated events. MRP4 was localized in post-acrosomal region and mid-piece at 15 min capacitation, while at 45 min it was mainly located in the acrosome. After 15 min, MK571 decreased total sperm motility (TM), progressive motility (PM) and several kinematic parameters. The addition of ecAMP rescued MK571 effect and ecAMP alone increased the percentage of motile sperm and kinematics parameters. Since actin cytoskeleton plays essential roles in the regulation of sperm motility, we investigated if MRP4 activity might affect actin polymerization. After 15 min capacitation, an increase in F-actin was observed, which was inhibited by MK571. This effect was reverted by the addition of ecAMP. Furthermore, ecAMP alone increased F-actin levels while no F-actin was detected with ecAMP in the presence of PKA inhibitors. Our results support the importance of cAMP efflux through MRP4 in sperm capacitation and suggest its involvement in the regulation of actin polymerization and motility.

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“…Paxillin is a multi-domain adaptor between the plasma membrane and the actin cytoskeleton [ 59 ] that serves as a docking protein for recruiting signaling molecules [ 60 ]. FAK is a cytoplasmic tyrosine kinase that localizes to FAs and regulates actin cytoskeleton remodeling for integrin-mediated processes such as cell spreading and migration [ 61 ], for example, by participating in actin polymerization [ 62 , 63 ]. The ‘force transduction layer’ contains mechanosensitive proteins such as talin and vinculin [ 64 , 65 ], which play key roles in mechanotransduction, as recent evidence suggests that talin is the key force-sensing molecule and vinculin one of the key mechanoeffectors [ 66 ].…”

Section: Proteins and Structures Involved In Stiffness Sensingmentioning

confidence: 99%

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

Selig

Lauer

Hart

et al. 2020

IJMS

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Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings. Ample evidence demonstrates that multiple molecular aspects of CH and mesenchymal stromal cell (MSC) phenotype are susceptible to material stiffness, because proliferation, migration, lineage determination, shape, cytoskeletal properties, expression profiles, cell surface receptor composition, integrin subunit expression, and nuclear shape and composition of CHs and/or MSCs are stiffness-regulated. Moreover, material stiffness modulates MSC immuno-modulatory and angiogenic properties, transforming growth factor beta 1 (TGF-β1)-induced lineage determination, and CH re-differentiation/de-differentiation, collagen type II fragment production, and TGF-β1- and interleukin 1 beta (IL-1β)-induced changes in cell stiffness and traction force. We then integrated the available molecular signaling data into a stiffness-regulated CH phenotype model. Overall, we recommend using material stiffness for controlling cell phenotype, as this would be a promising design cornerstone for novel future-oriented, cell-instructive biomaterials for clinical high-quality AC repair tissue.

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FAK regulates actin polymerization during sperm capacitation via the ERK2/GEF-H1/RhoA signaling pathway

Cited by 12 publications

References 90 publications

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Cyclic AMP efflux through MRP4 regulates actin dynamics signalling pathway and sperm motility in bovines

Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

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