There is no doubt that the DNA and chromosomes are considered to be the most exciting and important part of the cell nucleus. However, a vital and sometimes overlooked part of the cell nucleus is the nuclear lamina.
The term lamina is used in many fields including geology, botany, and physiology. Lamina (laminae – plural) means a very thin layer or plate. In geology it refers to the thinnest layer in a sedimentary rock that is different from other layers. In botany lamina can refer to a thin leaf or blade. In physiology lamina is used for the thin layers in bone. It is even used to describe the thin layers found in a horses hoof. In cell biology, lamina, specifically nuclear lamina refers to a complex mesh of intermediate fibers known as lamins and a number of lamin associated membrane proteins.
Among the lamin associated membrane proteins are: emerin, otefin, lamin B-receptor (LBR), lamin associated polypeptide 1 and 2 (LAP1 and LAP2) and MAN1 (also known as LEMD3). These proteins play an important role in the attachment of the nuclear lamina to the inner nuclear membrane.
Lamina is a dense fibrillar network that is associated with the inner layer of the nuclear membrane and measures between 30 to 100 nm thick. The lamins are often divided into A-type and B-type groupings. A-type lamins consist of A and C lamins, while B-type lamins consist of B1 and B2 lamins.
Studies have found that only 3 genes encode for lamins in all vertebrate species, whereas fruit flies only have 2 genes that code for lamins and a nematode (Caenorhabditis elegans) only has 1 gene for the coding for lamins.
Nuclear lamins are a V-type intermediate filaments which differ from cytoplasmic intermediate filaments by having an extended rod domain and that they carry a nuclear localization signal (NLS) at their C terminus.
Nuclear lamina functions include:
DNA replication. During the process of DNA replication, the DNA undergoes an elongation phase where the DNA is stretched out. Studies have indicated that the nuclear lamina provide a support structure for the DNA during this process. Additionally, there have been some indications that free lamin polypeptides may play part in a regulatory role during DNA replication.
Nuclear Support. The intermediate fibers that comprise part of the nuclear lamina, help provide structure and support to the nucleus similar to the way the intermediate fibers in the cytoplasm provide support and structure to the rest of the cell.
Chromatin organization. With the help of lamin polypeptides the nuclear lamina binds to the chromatin at matrix attachment regions (MAR) which are 300-1000 base pair sequences in the DNA.
Cell cycle regulation. At the beginning of mitosis, the nuclear lamina along with the nuclear membrane and pores start to breakdown, allowing for the chromosomes to intact and bind with the mitotic spindle. Then at the end of mitosis, these 3 structures reassemble to once again encapsulate the nuclear contents.
Cell development and differentiation. In embryonic studies of some birds and mammals, five different forms of lamin have been discovered: LI and LII considered to be similar to lamins B1 and B2; LIII considered to be similar to a B-type lamin; LA considered to be homologous to lamin type-A; and a fifth type that is specific to germ cells only. Lamins LI, LII and LIII (the B-type) appear to be expressed more in the earlier stages of embryonic development while the A and C-type lamins become significantly expressed in the later stages of development.
Apoptosis. Apoptosis, also known as cellular suicide involves the early breakdown of nuclear lamina. Without this step, the well coordinated apoptosis process would not continue.
Even though there may be only a few genes that code for nuclear lamina, various mutations to these genes are responsible for a number of human heritable diseases including:
- Emery-Dreifuss muscular dystrophy
- Limb girdle muscular dystrophy
- Dilated cardiomyopathy (DCM) with conduction system disease
- Familial partial lipodystrophy FPLD)
- Autosomal recessive axonal neuropathy (Charcot-Marie-Tooth disorder type 2, CMT2)
- mandibuloacral dysplasia (MAD)
- Hutchison Gilford Progeria syndrome (HGS)
- Greenberg Skeletal Dysplasia
- Pelger-Huet anomaly (PHA)
- Restrictive dermopathy
Nuclear lamina, originally thought to be nothing more than a nuclear skeletal support system is far more complex than this. It is a multifunctional key structure to the nucleus. Any defects in the nuclear lamina can be catastrophic to the overall heath of the organism as the list of diseases above illustrates.
Once again in our series on the Simple Cell, we see that every minute structure within the cell is anything but simple. Over and over this complexity demonstrates the impossibility of the evolution of a single cell, let alone an entire organism. Only the hands of our Creator God could have woven together the molecular intricacies of each and every cell.