Lamin

Lamins have elastic and mechanosensitive properties, and can alter gene regulation in a feedback response to mechanical cues.

[4] During this time period, investigations of rat liver nuclei revealed that lamins have an architectural relationship with chromatin and nuclear pores.

[8][9] Current research is being performed to develop treatment methods for the aforementioned laminopathies and to investigate the role lamins play in the aging process.

[2] These complex structures allow nuclear lamins to perform their specialized functions in maintaining the shape of the nucleus as well as roles during mitosis and apoptosis.

These subdivisions are based on similarities in cDNA sequences, structural features, isoelectric points, and expression trends.

[2][5] A-type lamins are characterized by a neutral isoelectric point, and they are typically displayed during later stages of embryonic development.

These steps include farnesylation of the carboxyl-terminal cysteine, endoproteolytic release of the terminal amino acids, carboxymethalation of the accessible farnesylcysteine, and removal of the final fifteen residues by a zinc metalloprotease.

[9][13] Some studies have demonstrated that lamins A and C are not required for the formation of the nuclear lamina, yet disruptions in the LMNA gene can contribute to physical and mental limitations.

This marker triggers the same sequence of posttranslational modifications previously described for prelamin A except for the final cleavage step involving a zinc metalloprotease.

These proteins in turn interact with cytoskeletal elements of the endoplasmic reticulum, forming a strong complex that can withstand mechanical stress.

[2] During mitosis, lamins are phosphorylated by Mitosis-Promoting Factor (MPF), which drives the disassembly of the lamina and the nuclear envelope.

[10] Mutations in the LMNA gene, encoding Lamins A and C, can produce a series of disorders ranging from muscular dystrophies, neuropathies, cardiomyopathies, and premature ageing syndromes.

Those affected by the condition appear normal at birth, but show signs of premature ageing including hair-loss, thinness, joint abnormalities, and weak motor skills as they develop.

Furthermore, health problems usually seen in older persons such as atherosclerosis and high blood pressure occur at a much younger age.

The genetic alteration results in an alternative splice, creating a mutated form of prelamin A that is much shorter and lacks the cleavage site for a zinc metalloprotease.

[3] Current studies are investigating the effects of farnesyl-transferase inhibitors (FTIs) to see if farnesyl attachment can be inhibited during posttranslational modification of prelamin A in order to treat patients with HGPS.