What can be concluded about lamin dynamics? a. While the nuclear lamina forms a tight network of proteins, individual lamina members, such as the lamin C proteins, are only partially bound to the lamina. b. A prominent pool of nucleoplasmic lamins exists in most cells, which interacts with intranuclear structures (DNA? Histones? Replication and/or transcription complexes?) in a dynamic fashion. c. During mitosis lamins do not play a key role in the initial reformation of the nuclear envelope. However, they are important for the correct functioning of the nucleus immediately after mitosis. Many questions remain unanswered, although nuclear lamins have been studied at different levels for over 20 years. We have only just begun to understand their crucial role in several cellular processes. Some of the important questions that still remain are: a. The function of intranuclear lamin foci. Are these native nuclear structures (nuclear channels/tubules) and do they play a role in replication and transcription? b. The function of the nucleoplasmic veil of lamins. Are these molecules only temporarily bound to intranuclear structures as a result of affinity to chromosomes or nuclear proteins, or is there a functional interaction with these molecules? c. The extent to which lamin molecules add to nuclear membrane organisation. Do these molecules play a key role in keeping the membrane intact and the nucleus functional, or are they only one of many supportive component of the nuclear membrane?
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Adv Protein Chem Struct Biol
January 2025
Genome Organisation and Dynamics Cluster, Center for Genome Engineering and Maintenance, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, London, United Kingdom. Electronic address:
The nuclear envelope has for long been considered more than just the physical border between the nucleoplasm and the cytoplasm, emerging as a crucial player in genome organisation and regulation within the 3D nucleus. Consequently, its study has become a valuable topic in the research of cancer, ageing and several other diseases where chromatin organisation is compromised. In this chapter, we will delve into its several sub-elements, such as the nuclear lamina, nuclear pore complexes and nuclear envelope proteins, and their diverse roles in nuclear function and maintenance.
View Article and Find Full Text PDFAdv Protein Chem Struct Biol
January 2025
Department of Medical Oncology (Lab), Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Electronic address:
Lamins, which are crucial type V intermediate filament proteins found in the nuclear lamina, are essential for maintaining the stability and function of the nucleus in higher vertebrates. They are classified into A- and B-types, and their distinct expression patterns contribute to cellular survival, development, and functionality. Lamins emerged during the transition from open to closed mitosis, with their complexity increasing alongside organism evolution.
View Article and Find Full Text PDFCirc Res
January 2025
British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, James Black Centre, King's College London, United Kingdom (C.Y.H., M.-Y.W., J.T., S.A., L.D., G.A., R.H., C.M.S.).
Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.
Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.
Nucleus
December 2025
Department of Physiology and Biophysics, The University of Illinois at Chicago - College of Medicine, Chicago, IL, USA.
The vascular network, uniquely sensitive to mechanical changes, translates biophysical forces into biochemical signals for vessel function. This process relies on the cell's architectural integrity, enabling uniform responses to physical stimuli. Recently, the nuclear envelope (NE) has emerged as a key regulator of vascular cell function.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Human Genetics, McGill University, 3666 McTavish Street, Montreal, QC H3A 1Y2, Canada.
Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells.
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