| Nuclear envelope | |
|---|---|
 Human cell nucleus | |
| Identifiers | |
| TH | H1.00.01.2.01001 |
| FMA | 63888 |
| Anatomical terminology | |
Thenuclear envelope, also known as thenuclear membrane,[1][a] is made up of twolipid bilayermembranes that ineukaryotic cells surround thenucleus, which encloses thegenetic material.
The nuclear envelope consists of two lipid bilayer membranes: an inner nuclear membrane and an outer nuclear membrane.[4] The space between the membranes is called the perinuclear space. It is usually about 10–50 nm wide.[5][6] The outer nuclear membrane is continuous with theendoplasmic reticulum membrane.[4] The nuclear envelope has manynuclear pores that allow materials to move between thecytosol and the nucleus.[4]Intermediate filament proteins calledlamins form a structure called thenuclear lamina on the inner aspect of the inner nuclear membrane and give structural support to the nucleus.[4]
The nuclear envelope is made up of two lipid bilayer membranes, an inner nuclear membrane and an outer nuclear membrane. These membranes are connected to each other by nuclear pores. Two sets of intermediate filaments provide support for the nuclear envelope. An internal network forms thenuclear lamina on the inner nuclear membrane.[7] A looser network forms outside to give external support.[4] The actual shape of the nuclear envelope is irregular. It has invaginations and protrusions and can be observed with anelectron microscope.
Theouter nuclear membrane also shares a common border with theendoplasmic reticulum.[8] While it is physically linked, the outer nuclear membrane contains proteins found in far higher concentrations than the endoplasmic reticulum.[9] All fournesprin proteins (nuclear envelopespectrin repeat proteins) present in mammals are expressed in the outer nuclear membrane.[10] Nesprin proteins connect cytoskeletal filaments to the nucleoskeleton.[11] Nesprin-mediated connections to the cytoskeleton contribute to nuclear positioning and to the cell’s mechanosensory function.[12]KASH domain proteins of Nesprin-1 and -2 are part of aLINC complex (linker of nucleoskeleton and cytoskeleton) and can bind directly to cystoskeletal components, such asactin filaments, or can bind to proteins in the perinuclear space.[13][14] Nesprin-3 and -4 may play a role in unloading enormous cargo; Nesprin-3 proteins bindplectin and link the nuclear envelope to cytoplasmic intermediate filaments.[15] Nesprin-4 proteins bind the plus end directed motor kinesin-1.[16] The outer nuclear membrane is also involved in development, as it fuses with the inner nuclear membrane to form nuclear pores.[17]
Theinner nuclear membrane encloses thenucleoplasm, and is covered by thenuclear lamina, a mesh ofintermediate filaments which stabilizes the nuclear membrane as well as being involved inchromatin function.[9] It is connected to the outer membrane bynuclear pores which penetrate the membranes. While the two membranes and the endoplasmic reticulum are linked, proteins embedded in the membranes tend to stay put rather than dispersing across the continuum.[18] It is lined with a fiber network called the nuclear lamina which is 10-40 nm thick and provides strength.[citation needed]
Mutations in thegenes that encode for theinner nuclear membrane proteins can cause severallaminopathies.[citation needed]
The nuclear envelope is punctured by around a thousandnuclear pore complexes, about 100 nm across, with an inner channel about 40 nm wide.[9] Thecomplexes contain a number ofnucleoporins, proteins that link the inner and outer nuclear membranes.[citation needed]
During theG2 phase ofinterphase, the nuclear membrane increases its surface area and doubles its number of nuclear pore complexes.[9]Ineukaryotes such asyeast which undergo closedmitosis, the nuclear membrane stays intact during cell division. Thespindle fibers either form within the membrane, or penetrate it without tearing it apart.[9]In other eukaryotes (animals as well as plants), the nuclear membrane must break down during theprometaphase stage of mitosis to allow themitotic spindle fibers to access the chromosomes inside. The breakdown and reformation processes are not well understood.
In mammals, the nuclear membrane can break down within minutes, following a set of steps during the early stages ofmitosis.First,M-Cdk's phosphorylatenucleoporinpolypeptides and they are selectively removed from the nuclear pore complexes. After that, the rest of the nuclear pore complexes break apart simultaneously. Biochemical evidence suggests that the nuclear pore complexes disassemble into stable pieces rather than disintegrating into small polypeptide fragments.[9] M-Cdk's also phosphorylate elements of the nuclear lamina (the framework that supports the envelope) leading to the disassembly of the lamina and hence the envelope membranes into small vesicles.[19]Electron andfluorescence microscopy has given strong evidence that the nuclear membrane is absorbed by the endoplasmic reticulum—nuclear proteins not normally found in the endoplasmic reticulum show up during mitosis.[9]
In addition to the breakdown of the nuclear membrane during the prometaphase stage ofmitosis, the nuclear membrane also ruptures in migrating mammalian cells during theinterphase stage of the cell cycle.[20] This transient rupture is likely caused by nuclear deformation. The rupture is rapidly repaired by a process dependent on "endosomal sorting complexes required for transport" (ESCRT) made up ofcytosolic protein complexes.[20] During nuclear membrane rupture events, DNA double-strand breaks occur. Thus the survival of cells migrating through confined environments appears to depend on efficient nuclear envelope andDNA repair machineries.
Aberrant nuclear envelope breakdown has also been observed in laminopathies and in cancer cells leading to mislocalization of cellular proteins, the formation of micronuclei and genomic instability.[21][22][23]
Exactly how the nuclear membrane reforms duringtelophase of mitosis is debated. Two theories exist[9]—
A study of the comparativegenomics,evolution and origins of the nuclear membrane led to the proposal that the nucleus emerged in the primitiveeukaryotic ancestor (the “prekaryote”), and was triggered by thearchaeo-bacterial symbiosis.[24] Several ideas have been proposed for the evolutionary origin of the nuclear membrane.[25] These ideas include the invagination of the plasma membrane in a prokaryote ancestor, or the formation of a genuine new membrane system following the establishment of proto-mitochondria in the archaeal host. The adaptive function of the nuclear membrane may have been to serve as a barrier to protect the genome fromreactive oxygen species (ROS) produced by the cells' pre-mitochondria.[26][27]
