Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.; Wehnert, Manfred; Hübner, Stefan

doi:10.1016/j.yexcr.2009.05.003

Cited by 50 publications

(47 citation statements)

References 70 publications

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“…It was clear that there was a significant (P,0.01) reduction in the number of NPCs on the surface of prelamin-A-accumulating nuclei compared with control nuclei. Additionally immunogold labelling revealed association of the Nup153 antibody (Busch et al, 2009) and mAb414 with the NR, supporting the notion that they contain at least certain key components of an NPC (Fig. 7d).…”

Section: Cct-a Forms Intanuclear Foci That Colocalise With Invaginatisupporting

confidence: 73%

“…They certainly cannot be normally functioning pores as both their sides face the nucleoplasm. The fact that there are many fewer Nup153-and mAb414-positive structures at the nuclear surface and an increased abundance of these nucleoporins localised inside the nucleus (Busch et al, 2009), in association with the NR, suggests that they are being drawn in by the invaginations. Their function could be a transcriptional one, as components of the NPC are being increasingly implicated as necessary components for initiating transcription (Capelson et al, 2010;Ikegami and Lieb, 2010;Kalverda et al, 2010;Vaquerizas et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…7). A recent study investigated the effect on the distribution of Nup153 in cells expressing nuclear envelopathy-causing lamin A mutants and found it to be highly disorganised (Busch et al, 2009). The Nup153 protein is located in the basket of NPC, but reported to be a dynamic nucleoporin (Daigle et al, 2001).…”

Section: Cct-a Forms Intanuclear Foci That Colocalise With Invaginatimentioning

confidence: 99%

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The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Goulbourne

Malhas

Vaux

2011

Journal of Cell Science

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SummaryFarnesylated prelamin A accumulates when the final endoproteolytic maturation of the protein fails to occur and causes a dysmorphic nuclear phenotype; however, the morphology and mechanisms of biogenesis of these changes remain unclear. We show here that acute prelamin A accumulation after reduction in the activity of the ZMPSTE24 endoprotease by short interfering RNA knockdown, results in the generation of a complex nucleoplasmic reticulum that depends for its formation on the enzyme CTP:phosphocholinecytidylyltransferase-a (CCT-a, also known as choline-phosphate cytidylyltransferase A). This structure can form during interphase, confirming that it is independent of mitosis and therefore not a consequence of disordered nuclear envelope assembly. Serial-section dual-axis electron tomography reveals that these invaginations can take two forms: one in which the inner nuclear membrane infolds alone with an inter membrane space interior, and the other in which an invagination of both nuclear membranes occurs, enclosing a cytoplasmic core. Both types of invagination can co-exist in one nucleus and both are frequently studded with nuclear pore complexes (NPC), which reduces NPC abundance on the nuclear surface.

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Section: Cct-a Forms Intanuclear Foci That Colocalise With Invaginatisupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Cct-a Forms Intanuclear Foci That Colocalise With Invaginatimentioning

confidence: 99%

See 1 more Smart Citation

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Goulbourne

Malhas

Vaux

2011

Journal of Cell Science

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“…Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: is a recessively inherited syndrome of aging causing death by 2 years [3]. Other syndromes (e.g., Down, Ehlers-Danlos) occasionally have progeroid features [10]- [12]. Acquired VWD is usually associated with an underlying disorder, e.g.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Diseases and Acquired Von Willebrand Disease in Two Cases of Progeria

Alshok¹

2014

IJCM

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Ammar A., a 23-year-old male patient, who lives in Babylon, Haswa District, and his mother describes symptoms of growth retardation, skin changes, hair changes early graying and alopecia. These manifestation started early during his childhood period. There is canseguanity between the patient's mother & father also one of the patient's sister has similar illness and one male brother died few months following his birth. We admit the patient to hospital due acute pulmonary infection in Jan 2009, which is controlled after a course of antibiotic and after 5 months he develops generalised mucocuteneous bullous eruption which shows partial response to oral prednisolone 2 mg/Kg. The patient has normal IQ and he is in the secondary school and he has normal blood picture and the only abnormal biochemical abnormalities is mild hyperlipidemia Serum cholestrol of 5.8 mmol/L and Serum Triglyceride of 260 mg/dl. Ammar's Sister Qawthar A., who has a similar phenotypic manifestations, presented skin vitiligo and hepatosplenomegaly associated with sever anemia and jaundice and her presentation suggestive of autoimmune haemolytic anemia improved following blood transfusion, corticosteroid and azothioprim. In February 2014 Ammer presented with multiple and diffuse cuteneous ecchymymosis with markedly prolonged PTT and slightly proloned bleeding time highly consistent with acquired Von Willebrand's disease. In conclusion premature aging is a predisposing factor for disturbed immunity and development of autoimmune diseases.

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“…These mutations reduce the population of Nup153 present at the NE maybe by impairing Nup153-lamin interaction or by promoting accumulation of Nup153 at mutated lamin A aggregates (Hübner et al, 2006). This lack of Nup153 at the nuclear periphery might contribute to a compromised nuclear protein import (Busch et al, 2009).…”

Section: Nup153-related Disordersmentioning

confidence: 99%

The nuclear pore complex: structure and function

Duhéron¹,

Fahrenkrog²

2017

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Forkhead box P3 (FOXP3), a gene member of the forkhead/winged-helix family of transcription regulators, is Nuclear pore complexes (NPCs) are large multi-protein complexes, which are embedded in the nuclear envelope and which are regulating the molecular exchange between the nucleus and the cytoplasm. While electron microscopy and cryo-electron tomography studies have provided high-resolution pictures of the NPC structure as entity, the challenge nowadays is to elucidate the organization and the functions of nuclear pore proteins (nucleoporins or Nups) inside and outside the NPC. Nucleoporins are not only involved in nucleocytoplasmic transport, but in an increasing number of other cellular processes, such as kinetochore organization, cell cycle regulation, DNA repair, and gene expression. The implication of nucleoporins in these diverse processes links them also to a wide variety of human diseases, such as cancer and autoimmune diseases. Here we review the progress made in defining the molecular arrangement of nucleoporins within the NPC and use the example of Nup153 to illustrate the versatility of individual nucleoporins and their implication in various human diseases.

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Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

Cited by 50 publications

References 70 publications

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-α

Autoimmune Diseases and Acquired Von Willebrand Disease in Two Cases of Progeria

The nuclear pore complex: structure and function

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