Lamin

analysis of a dermal fibroblast in primary culture from a control (a and b) and the subject with HGPS (c and d). Labelling was performed with anti-lamin A/C antibodies. Note the presence of irregularly shaped nuclear envelopes in many of the subject's fibroblasts Lamins, also known as nuclear lamins, are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. Lamins have elastic and mechanosensitive properties, and can alter gene regulation in a feedback response to mechanical cues. Lamins are present in all animals but are not found in microorganisms, plants or fungi. Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. Mutations in lamin genes can result in several genetic laminopathies, which may be life-threatening.

analysis of a dermal fibroblast in primary culture from a control (a and b) and the subject with HGPS (c and d). Labelling was performed with anti-lamin A/C antibodies. Note the presence of irregularly shaped nuclear envelopes in many of the subject's fibroblasts Lamins, also known as nuclear lamins, are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. Lamins have elastic and mechanosensitive properties, and can alter gene regulation in a feedback response to mechanical cues. Lamins are present in all animals but are not found in microorganisms, plants or fungi. Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. Mutations in lamin genes can result in several genetic laminopathies, which may be life-threatening.

A- and B-types

Lamins are divided into two major categories: A- and B-types. These subdivisions are based on similarities in cDNA sequences, structural features, isoelectric points, and expression trends.

Function

Hutchinson-Gilford progeria syndrome

One specific laminopathy is Hutchinson-Gilford progeria syndrome (HGPS), characterized by premature ageing. 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. Those with HGPS typically die in their early teens, usually following a heart attack or stroke. HGPS is caused by a point mutation in the LMNA gene that codes for lamin A. 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. Because prelamin A cannot be properly processed during posttranslational modifications, it retains its lipid modification (farnesylation) and remains in the inner nuclear membrane. This disrupts the mechanical stability of the nucleus, resulting in a higher rate of cell death and therefore a higher rate of aging. 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.

References

External links

Text derived from https://en.wikipedia.org/w/index.php?oldid=1376072650 under CC BY-SA 4.0; modifications have been made.