Actin on and around the Nucleus Davidson, Patricia M.; Cadot, Bruno
Trends in cell biology,
March 2021, 2021-Mar, 2021-03-00, 20210301, 2021-03, Letnik:
31, Številka:
3
Journal Article
Recenzirano
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Actin plays roles in many important cellular processes, including cell motility, organelle movement, and cell signaling. The discovery of transmembrane actin-binding proteins at the outer nuclear ...membrane (ONM) raises the exciting possibility that actin can play a role in direct force transmission to the nucleus and the genome at its interior. Actin-dependent nucleus displacement was first described a decade ago. We are now gaining a more detailed understanding of its mechanisms, as well as new roles for actin during mitosis and meiosis, for gene expression, and in the cell’s response to mechanical stimuli. Here we review these recent developments, the actin-binding proteins involved, the tissue specificity of these mechanisms, and methods developed to reconstitute and study this interaction in vitro.
Direct connections between the actin cytoskeleton and the nucleus govern nuclear positioning, nuclear movement during cell polarization and migration, nuclear movement before and after mitosis and meiosis, nuclear envelope breakdown, mechanotransduction, and gene expression.The nucleus directly connects to actin through transmembrane proteins (LINC complex proteins) complemented by a large family of actin-associated proteins that interact with proteins of the nuclear envelope.Actin can act indirectly on the nucleus to displace it, to protect it from external forces, and to dampen mechanical stimuli. However, the compression exerted by actin can cause nuclear rupture.Interactions between the nucleus and actin are studied in vitro using isolated nuclei and reconstituted actin networks.
During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, which requires extensive deformation of the cell and its nucleus. Here, we investigated mammalian tumor cell ...migration in confining microenvironments in vitro and in vivo. Nuclear deformation caused localized loss of nuclear envelope (NE) integrity, which led to the uncontrolled exchange of nucleo-cytoplasmic content, herniation of chromatin across the NE, and DNA damage. The incidence of NE rupture increased with cell confinement and with depletion of nuclear lamins, NE proteins that structurally support the nucleus. Cells restored NE integrity using components of the endosomal sorting complexes required for transport III (ESCRT III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival.
Highlights • Lamins modulate nuclear mechanics, chromatin organization, and gene regulation. • Lamin mutations cause a broad spectrum of diseases with often tissue-specific defects. • Lamin mutations ...can disrupt nuclear stability and nucleo-cytoskeletal connections. • Lamins play an important role in mechanosensing and mechanotransduction signaling. • Many cancers have altered lamin expression, and this may facilitate metastatic spreading.
Background:
The majority of expected deaths occur in hospitals where optimal end-of-life care is not yet fully realised, as evidenced by recent reviews outlining experience of care. Better ...understanding what patients and their families consider to be the most important elements of inpatient end-of-life care is crucial to addressing this gap.
Aim and design:
This systematic review aimed to ascertain the five most important elements of inpatient end-of-life care as identified by patients with palliative care needs and their families.
Data sources:
Nine electronic databases from 1990 to 2014 were searched along with key internet search engines and handsearching of included article reference lists. Quality of included studies was appraised by two researchers.
Results:
Of 1859 articles, 8 met the inclusion criteria generating data from 1141 patients and 3117 families. Synthesis of the top five elements identified four common end-of-life care domains considered important to both patients and their families, namely, (1) effective communication and shared decision making, (2) expert care, (3) respectful and compassionate care and (4) trust and confidence in clinicians. The final domains differed with financial affairs being important to families, while an adequate environment for care and minimising burden both being important to patients.
Conclusion:
This review adds to what has been known for over two decades in relation to patient and family priorities for end-of-life care within the hospital setting. The challenge for health care services is to act on this evidence, reconfigure care systems accordingly and ensure universal access to optimal end-of-life care within hospitals.
SARS-CoV-2, the virus that causes COVID-19, is wreaking havoc around the world. This unprecedented pandemic has led to illness, death, and economic destruction. The pandemic has challenged health ...care systems globally for a range of reasons. In developed economies the focus on non-communicable diseases rather than infectious diseases have caught us short. A period of complacency and a lack of focus on potential pandemics has meant that documented shortages of personnel, workforce and equipment has limited healthcare delivery.
Abstract Context Chronic obstructive pulmonary disease (COPD) is a life-limiting illness. Despite best available treatments, individuals continue to experience symptom burden and have high health ...care utilization. Objectives To increase understanding of the experience and ongoing needs of individuals living with COPD. Methods Medline, PsycINFO, CINAHL, and Sociological Abstracts were searched for articles published between January 1990 and June 2013. Metasynthesis of qualitative data followed the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Metasyntheses are increasingly used to gain understandings of complex research questions through synthesizing data from individual qualitative studies. Descriptive and analytical themes were developed through thematic synthesis and expert panel discussion of extracted primary quotes, not the primary data themselves. Results Twenty-two studies were included. Four hundred twenty-two free codes were condensed into seven descriptive themes: better understanding of condition, breathlessness, fatigue, frailty, anxiety, social isolation, and loss of hope and maintaining meaning. These seven themes were condensed further into three analytical themes that described the experience and ongoing needs of individuals with COPD: the need for better understanding of condition, sustained symptom burden, and the unrelenting psychological impact of living with COPD. Conclusion Combining discrete qualitative studies provided a useful perspective of the experience of living with COPD over the past two decades. Further studies into the ongoing needs of individuals with COPD are unlikely to add to this well-established picture. Future research should focus on solutions through the development of interventions that address patients' ongoing needs.
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