scholarly journals Accessorizing and anchoring the LINC complex for multifunctionality

2015 ◽  
Vol 208 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Wakam Chang ◽  
Howard J. Worman ◽  
Gregg G. Gundersen
Keyword(s):  
Nuclear Membrane ◽  
Meiotic Chromosome ◽  
Linc Complex ◽  
Factors Associated ◽  
Ordered Arrays ◽  
Anchoring Proteins ◽  
Core Components ◽  
Chromosome Movements ◽  
Shed Light

The linker of nucleoskeleton and cytoskeleton (LINC) complex, composed of outer and inner nuclear membrane Klarsicht, ANC-1, and Syne homology (KASH) and Sad1 and UNC-84 (SUN) proteins, respectively, connects the nucleus to cytoskeletal filaments and performs diverse functions including nuclear positioning, mechanotransduction, and meiotic chromosome movements. Recent studies have shed light on the source of this diversity by identifying factors associated with the complex that endow specific functions as well as those that differentially anchor the complex within the nucleus. Additional diversity may be provided by accessory factors that reorganize the complex into higher-ordered arrays. As core components of the LINC complex are associated with several diseases, understanding the role of accessory and anchoring proteins could provide insights into pathogenic mechanisms.

scholarly journals Coupling of the nucleus and cytoplasm: Role of the LINC complex

2005 ◽  
Vol 172 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Melissa Crisp ◽  
Qian Liu ◽  
Kyle Roux ◽  
J.B. Rattner ◽  
Catherine Shanahan ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Integral Membrane Proteins ◽  
Actin Binding ◽  
Linc Complex ◽  
Outer Membranes ◽  
Perinuclear Space ◽  
Actin Binding Domain ◽  
Lumenal Domain ◽  
Integral Proteins

The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419–3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).

scholarly journals A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Manickam Gurusaran ◽  
Owen Richard Davies
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanism ◽  
Complex Network ◽  
Meiotic Chromosome ◽  
Force Distribution ◽  
The Sun ◽  
Linc Complex ◽  
Cellular Functions ◽  
Zinc Coordination ◽  
Chromosome Movements

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing, and meiotic chromosome movements. The canonical model is that 3:3 interactions between SUN and KASH proteins underlie the nucleocytoskeletal linkages provided by the LINC complex. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 interface provides a molecular mechanism for the establishment of integrative and distributive connections between 3:3 structures within a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

scholarly journals A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

2020 ◽  
Author(s):  
Manickam Gurusaran ◽  
Owen R. Davies
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanism ◽  
Meiotic Chromosome ◽  
Current Model ◽  
Force Distribution ◽  
The Sun ◽  
Linc Complex ◽  
Cellular Functions ◽  
Zinc Coordination ◽  
Chromosome Movements

SummaryThe LINC complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 complex is incompatible with the current model of a linear LINC complex and instead suggests the formation of a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

The Role of Zinc in Thyroid Hormones Metabolism

2019 ◽  
Vol 89 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Juliana Soares Severo ◽  
Jennifer Beatriz Silva Morais ◽  
Taynáh Emannuelle Coelho de Freitas ◽  
Ana Letícia Pereira Andrade ◽  
Mayara Monte Feitosa ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Scientific Evidence ◽  
Thyroid Stimulating Hormone ◽  
Zinc Transporters ◽  
Serum Concentrations ◽  
Metabolic Adaptations ◽  
Serum T3 ◽  
Regulatory Effects ◽  
Shed Light

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.

The Adult as Foe or Friend?: Childism in Guus Kuijer's Criticism and Fiction

2013 ◽  
Vol 6 (2) ◽  
pp. 205-217 ◽  
Author(s):  
Vanessa Joosen
Keyword(s):  
Children's Literature ◽  
Children’S Literature ◽  
Age Groups ◽  
Children's Books ◽  
Children’S Books ◽  
Memorial Award ◽  
Adult Reader ◽  
Shed Light ◽  
Selection Of

Compared to the attention that children's literature scholars have paid to the construction of childhood in children's literature and the role of adults as authors, mediators and readers of children's books, few researchers have made a systematic study of adults as characters in children's books. This article analyses the construction of adulthood in a selection of texts by the Dutch author and Astrid Lindgren Memorial Award winner Guus Kuijer and connects them with Elisabeth Young-Bruehl's recent concept of ‘childism’ – a form of prejudice targeted against children. Whereas Kuijer published a severe critique of adulthood in Het geminachte kind [The despised child] (1980), in his literary works he explores a variety of positions that adults can take towards children, with varying degrees of childist features. Such a systematic and comparative analysis of the way grown-ups are characterised in children's texts helps to shed light on a didactic potential that materialises in different adult subject positions. After all, not only literary and artistic aspects of children's literature may be aimed at the adult reader (as well as the child), but also the didactic aspect of children's books can cross over between different age groups.

Tax evasion in the medical profession An Empirical Study in the General Tax Authority in Iraq

2019 ◽  
Vol 118 (11) ◽  
pp. 80-88
Author(s):  
Ramyar Rzgar Ahmed ◽  
Hawkar Qasim Birdawod ◽  
S. Rabiyathul Basariya
Keyword(s):  
Tax Evasion ◽  
Income Tax ◽  
Medical Profession ◽  
Great Influence ◽  
Tax Law ◽  
Degree Of Confidence ◽  
Medical Professions ◽  
Shed Light

The study dealt with tax evasion in the medical profession, where the problem was the existence of many cases of tax evasion, especially tax evasion in the income tax of medical professions. The aim of the study is to try to shed light on the phenomenon of tax evasion and the role of the tax authority in the development of controls and means that reduce the phenomenon of tax evasion. The most important results of the low level of tax awareness and lack of knowledge of the tax law and the unwillingness to read it and the sense of taxpayers unfairness of the tax all lead to an increase in cases of tax evasion and in suggested tightening control and follow-up on the offices of auditors, through the investigation and auditing The reports of certified accountants and the use of computers for this purpose in order to raise the degree of confidence in these reports and bring them closer to the required truth and coordination and cooperation with the Union of Accountants and Auditors and inform them about each case of violations of the auditors and accountants N because of its great influence in the rejection of the organization of the accounts and not to ratify fake accounts lead to show taxpayers accounts on a non-truth in order to tax evasion.

The Baluch, Sunnism and the State in Iran

2017 ◽  
Author(s):  
Stéphane A. Dudoignon
Keyword(s):  
South Asia ◽  
South Asian ◽  
Social Life ◽  
The State ◽  
First Century ◽  
Local Democracy ◽  
Oasis Area ◽  
Shed Light

Since 2002, Sunni jihadi groups have been active in Iranian Baluchistan without managing to plunge the region into chaos. This book suggests that a reason for this, besides Tehran’s military responses, has been the quality of Khomeini and Khamenei’s relationship with a network of South-Asia-educated Sunni ulama (mawlawis) originating from the Sarbaz oasis area, in the south of Baluchistan. Educated in the religiously reformist, socially conservative South Asian Deoband School, which puts the madrasa at the centre of social life, the Sarbazi ulama had taken advantage, in Iranian territory, of the eclipse of Baluch tribal might under the Pahlavi monarchy (1925-79). They emerged then as a bulwark against Soviet influence and progressive ideologies, before rallying to Khomeini in 1979. Since the turn of the twenty-first century, they have been playing the role of a rampart against Salafi propaganda and Saudi intrigues. The book shows that, through their alliance with an Iranian Kurdish-born Muslim-Brother movement and through the promotion of a distinct ‘Sunni vote’, they have since the early 2000s contributed towards – and benefitted from – the defence by the Reformist presidents Khatami (1997-2005) and Ruhani (since 2013) of local democracy and of the minorities’ rights. They endeavoured to help, at the same time, preventing the propagation of jihadism and Sunni radicalisation to Iran – at least until the ISIS/Daesh-claimed attacks of June 2017, in Tehran, shed light on the limits of the Islamic Republic’s strategy of reliance on Deobandi ulama and Muslim-Brother preachers in the country’s Sunni-peopled peripheries.

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