Zygotic Nuclear F-Actin Safeguards Embryonic Development

Okuno, Tomomi; Li, Wayne Yang; Hatano, Yu; Takasu, Atsushi; Sakamoto, Yuko; Yamamoto, Masanobu; Ikeda, Zenki; Shindo, Taiki; Plessner, Matthias; Morita, Kohtaro; Matsumoto, Kazuya; Yamagata, Kazuya; Grosse, Robert; Miyamoto, Kazuaki

doi:10.1016/j.celrep.2020.107824

Cited by 41 publications

(43 citation statements)

References 66 publications

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“…One possible explanation for the gradual increase in the nuclear size is that nuclear swelling is mediated by a recently found player, nuclear actin ( Baarlink et al., 2017 ; Wei et al., 2020 ). We have shown that pronuclear volume is reduced when nuclear actin is depolymerized ( Okuno et al., 2020 ). Furthermore, in the cultured cells, nuclear swelling and chromatin decondensation after mitosis are mediated by nuclear actin assembly ( Baarlink et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Cell division- and DNA replication-free reprogramming of somatic nuclei for embryonic transcription

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Cell division- and DNA replication-free reprogramming of somatic nuclei for embryonic transcription

et al. 2021

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“…[7,22,23] This includes light-regulatable nuclear protein export using the LEXY system to shuttle the small actin filament severing and disassembly factor Cofilin-1 in and out of the nucleus. [24,38] Here we applied the LEXY system to a relatively large protein and to an actin-regulated transcription factor MRTF-A. MRTF-A shuttles between cytoplasmic and nuclear compartment in an actin-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic Control of Myocardin‐Related Transcription Factor A Subcellular Localization and Transcriptional Activity Steers Membrane Blebbing and Invasive Cancer Cell Motility

Zhao

Grosse

2021

Advanced Biology

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Similar to SRF, its coactivator MRTF-A (also known as MAL or MKL1) is ubiquitously expressed and controls actin-associated gene expression for numerous functions in development and disease as well as many cell migratory processes. [3,4] The latter occurs largely via the regulation of cytoskeletal genes following signal-induced MRTF-A nuclear translocation. [5][6][7] Notably, MRTF-A dependent immediate gene expression appears to be the predominant cellular SRF transcriptional response to extracellular signals such as serum. [8] In addition, it is now well established that MRTF-A transcriptional activity is an important driver of tumor progression by promoting invasion and metastasis. [9][10][11][12][13][14][15][16] We could recently show that MRTF-A activity promotes non-apoptotic plasma membrane (PM) blebbing often observed during blebassociated invasive cell migration. [17] This MRTF-A nuclear activity was in turn triggered by PM blebbing thereby facilitating a positive feedback loop to drive PM dynamics and cell motility through MRTF-SRF transcription. [17] Such mechanism is consistent with the fact that nuclear localization of MRTF-A depends on actin dynamics. [5] This occurs via three core RPEL actin-binding sites (R1-R3) and the two spacer actin-binding regions (S1, S2) within the N-terminus of MRTF-A (Figure 1A). [18] Specifically, the RPEL domain of MRTF-A interacts with actin such that binding of all five actin monomers (G-actin) promotes MRTF-A nuclear export while dissociation of the G-actin molecules favors its Nuclear localization signal (NLS)-dependent nuclear import (Figure 1A). [18] This mechanism allows MRTF-A to sense and rapidly respond to changes in actin dynamics resulting in the regulation of gene expression. [19] Nucleocytoplasmic shuttling is regarded as an essential mechanism to control the activity of transcriptional factors. [20] Quite recently, a few optogenetic tools have been generated to artificially manipulate the localization of nuclear proteins, [21] providing a new perspective for modulating cellular activities. Here, we devised and employed an optogenetic strategy using the modified light-oxygen-voltage-sensing domain 2 (LOV2) LEXY to spatiotemporally control MRTF-A nuclear localization and function independently of actin dynamics. Optogenetic The myocardin-related transcription factor A (MRTF-A) controls the transcriptional activity of the serum response factor (SRF) in a tightly controlled actin-dependent manner. In turn, MRTF-A is crucial for many actin-dependent processes including adhesion, migration, and contractility and has emerged as a novel target for anti-tumor strategies. MRTF-A rapidly shuttles between cytoplasmic and nuclear compartment via dynamic actin interactions within its N-terminal RPEL domain.Here, optogenetics is used to spatiotemporally control MRTF-A nuclear localization by blue light using the light-oxygen-voltage-sensing domain 2-domain based system LEXY (light-inducible nuclear export system). It is found that lightregulated nuclear export of MRTF-A o...

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“…This dual localization is required for maximal transcription; in fact, in the nucleus, actin regulates the activity of specific transcription factors, participates in several chromatin remodeling complexes, and associates with all three RNA polymerases [ 89 ]. Intriguingly, nuclear filamentous actin (F-actin) has been found after fertilization in zygote, inside the large and decondensed pronuclei [ 90 ]. It is required for fully functional pronuclei; in fact, its perturbation causes the mis-regulation of genes related to genome integrity, generating an abnormal development of mouse embryos [ 90 ].…”

Section: The Role Of the Linc Complex In Mechanotransductionmentioning

confidence: 99%

“…Intriguingly, nuclear filamentous actin (F-actin) has been found after fertilization in zygote, inside the large and decondensed pronuclei [ 90 ]. It is required for fully functional pronuclei; in fact, its perturbation causes the mis-regulation of genes related to genome integrity, generating an abnormal development of mouse embryos [ 90 ].…”

Section: The Role Of the Linc Complex In Mechanotransductionmentioning

confidence: 99%

LINCking the Nuclear Envelope to Sperm Architecture

Manfrevola

Guillou

Fasano

et al. 2021

Genes

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Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility.

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Zygotic Nuclear F-Actin Safeguards Embryonic Development

Abstract: Highlights d Filamentous actin is a hallmark of pronuclei in mouse zygotes d Polymerized nuclear actin is important for embryonic development d Zygotic nuclear F-actin is required for efficient DNA damage repair d The timely disassembly of nuclear F-actin is key to subsequent development

Cited by 41 publications

References 66 publications

Cell division- and DNA replication-free reprogramming of somatic nuclei for embryonic transcription

Cell division- and DNA replication-free reprogramming of somatic nuclei for embryonic transcription

Optogenetic Control of Myocardin‐Related Transcription Factor A Subcellular Localization and Transcriptional Activity Steers Membrane Blebbing and Invasive Cancer Cell Motility

LINCking the Nuclear Envelope to Sperm Architecture

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