Perinuclear space

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Editor-In-Chief: Henry A. Hoff

The space between the inner and outer nuclear membranes is called the perinuclear space. The perinuclear space (PNS) is joined with the lumen of the rough endoplasmic reticulum (RER). Width of the perinuclear space is about 20 - 40 nm. The perinulcear space is also called the perinuclear cisterna or nuclear envelope lumen.

Nuclear envelope

The nuclear envelope has two membranes, each with the typical unit membrane structure. They enclose a flattened sac (PNS) and are connected at the nuclear pore sites. The outermost membrane is continuous with the rough endoplasmic reticulum and has ribosomes attached. The space between the outer and inner membranes is also continuous with rough endoplasmic reticulum space. It can fill with newly synthesized proteins just as the rough endoplasmic reticulum does. The nuclear envelope is enmeshed in a network of filaments for stability.

The inner nuclear membrane is the primary residence of several inner nuclear membrane proteins. The outer and inner nuclear membrane are fused at the site of nuclear pore complex insertion.

The perinuclear space between the two membranes that make up the nuclear envelope is also called the perinuclear cisterna, NE Lumen, and is usually about 20 - 40 nm wide.

Nuclear envelope membrane skeleton

The protein enaptin is made up of three main parts: cytoplasmic (1-8746), anchor for type IV membrane protein (8747-8767), and the sequence for perinuclear space (8768-8797). The region in the perinuclear space contains a KASH domain (Klarsicht, ANC-1, Syne Homology). The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to disappear after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes).[1]

Nesprin is a protein that is found in the outer nuclear membrane. It attaches to the actin filaments of the cytoskeleton and to emerin which is found in the inner nuclear membrane.

Emerin 18 kDa (no NLS) mediates inner nuclear membrane anchorage to the nuclear lamina, regulates the flux of beta-catenin into the nucleus, and interacts with nuclear actin.[2][3][4]

The C-terminal of the KASH domain contains a single transmembrane segment, followed by an evolutionarily conserved sequence (9–32 amino acids), located in the PNS (perinuclear space).

Most proteins containing KASH domains may be involved in the positioning of the nucleus in the cell. These domains may interact with proteins containing SUN domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope and transfer force from the nucleoskeleton to the cytoskeleton.

Like proteins containing KASH domains most proteins containing SUN domains may be involved in the positioning of the nucleus in the cell. SUN domains may interact directly with KASH domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope and transfer force from the nucleoskeleton to the cytoskeleton. SUN proteins may preferentially localize to the inner nuclear membrane[5]. Although KASH proteins probably localize to the outer nuclear membrane, some KASH protein isoforms may localize to the inner nuclear membrane.[6]

Functions of the perinuclear space

Studies of the ultrastructure of chick embryo somite cells indicate the presence of ribosome-like granules in polysome-like configurations in the perinuclear space within nuclear blebs (average size ~240 x 300 nm).[7] Some of the blebs are contiguous with elements of the endoplasmic reticulum, while the lumen of others is continuous with the lumen of tubules of endoplasmic reticulum.[7]

The perinuclear space contains a fine-grained, massive electron-dense protein-rich secretion.[8]

Electron microscopic examination of exocrine pancreatic tissues from the fish Scorpaena scrofa L. shows that zymogenic vesicles can be extruded from the perinuclear space and it confirms the suspected, synthetic activity of this cell compartment.[9]

Endoplasmic reticulum

The endoplasmic reticulum (ER) is a membranous synthesis and transport organelle that is an extension of the nuclear envelope. More than half the total membrane in eukaryotic cells is accounted for by the ER. The ER is made up of flattened sacs and branching tubules that are thought to interconnect, so that the ER membrane forms a continuous sheet enclosing a single internal space. This highly convoluted space is called the ER lumen and is also referred to as the ER cisternal space. The lumen takes up about ten percent of the entire cell volume. The endoplasmic reticulum membrane allows molecules to be selectively transferred between the lumen and the cytoplasm, and since it is connected to the nuclear envelope, it provides a channel between the nucleus and the cytoplasm.[10]

The general structure of the endoplasmic reticulum is an extensive membrane network of cisternae (sac-like structures) held together by the cytoskeleton. The phospholipid membrane encloses a space, the cisternal space (or lumen), from the cytosol.

The smooth endoplasmic reticulum (SER) has functions in several metabolic processes, including synthesis of lipids and steroids, metabolism of carbohydrates, regulation of calcium concentration, drug detoxification, attachment of receptors on cell membrane proteins, and steroid metabolism.[11] It is connected to the nuclear envelope. The only structural difference between the sarcoplasmic reticulum and the SER is the medley of proteins they have, both bound to their membranes and drifting within the confines of their lumens.

Infections of the perinuclear space

After the Mardivirus enters the cell the nucleocapsid makes its way to a nuclear pore where the virus genome is released and translocates into the nucleus. The virus genome replicates and is packaged up within the nucleus. This new nucleocapsid then buds from the inner nuclear membrane and so gains its primary envelope. The nucleocapsid is now in the perinuclear space in the endoplasmic reticulum, from here the nucleocapsid buds from the outer nuclear membrane and by an unknown mechanism loses its primary envelope leaving the nucleocapsid naked in the cytoplasm.[12]

Endoplasmic reticulum stress response

XBP-1 is upregulated as part of the endoplasmic reticulum (ER) stress response, the unfolded protein response (UPR).[13] This increase in transcription requires an ER stress response consensus binding element in the promoter. XBP-1u is ubiquitously expressed but under conditions of ER-stress, the XBP-1u mRNA is processed by IRE1. Activated IRE1 oligomerises and activates its ribonuclease domain through auto (self) phosphorylation. Because the lumen of the ER is continuous with the perinuclear space, the activated ribonuclease domains can penetrate the inner leaflet of the nuclear envelope. Within the nucleus, activated IRE1 catalyses the excision of a 26 nucleotide unconventional intron from XBP-1 mRNA, in a manner mechanistically similar to pre-tRNA splicing. Removal of this intron causes a frame shift in the XBP-1 coding sequence resulting in the translation of a 371 amino acid, 54 kDa, XBP-1s isoform rather than the 261 amino acid, 33 kDa, XBP-1u isoform.

Clinical signficance

A single nucleotide polymorphism, C-116G, in the promoter region of XBP1 has been examined for possible association with personality traits. None was found.[14]

Abnormalities in XBP1 lead to a heightened ER stress and subsequently causes a heightened susceptibility for inflammatory processes.

Specifically in the colon, XBP1 anomalies have been linked to Crohn's disease.[15]

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikipedia.

References

  1. "ProtParam SYNE1_HUMAN (Q8NF91)".
  2. "Entrez Gene: EMD emerin".
  3. "GENATLAS: GENE Database EMD".
  4. "Apropos IpiRecord: IPI00032003".
  5. Tzur YB, Wilson KL, Gruenbaum Y (2006). "SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton". Nat Rev Mol Cell Biol. 7 (10): 782–8. doi:10.1038/nrm2003. PMID 16926857. Unknown parameter |month= ignored (help)
  6. Starr DA, Fischer JA (2005). "KASH 'n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins". Bioessays. 27 (11): 1136–46. doi:10.1002/bies.20312. PMID 16237665. Unknown parameter |month= ignored (help)
  7. 7.0 7.1 Weston JC (1968). "Ribosome-like granules within areas of the perinuclear space in cells of 13–14 somite chick embryos". Cell Tiss Res. 87 (2): 199–209. doi:10.1007/BF00319719. Unknown parameter |month= ignored (help)
  8. Sterba G, Kabisch K, Schneider B, Hoheisei (1972). "Storing of secretory material inside the perinuclear space". Cell Mole Life Sci. 28 (8): 934–6. doi:10.1007/BF01924957. Unknown parameter |month= ignored (help)
  9. Gilloteaux J, Kashouty R, Yono N (2008). "The perinuclear space of pancreatic acinar cells and the synthetic pathway of zymogen in Scorpaena scrofa L.: Ultrastructural aspects". Tiss Cell. 40 (1): 7–20. doi:10.1016/j.tice.2007.08.004. Unknown parameter |month= ignored (help)
  10. Cooper, Geoffrey (2000). "The Endoplasmic Reticulum". The Cell: A Molecular Approach. Sinauer Associates, Inc. Retrieved 2008-12-09.
  11. Maxfield FR, Wüstner D (2002). "Intracellular cholesterol transport". J Clin Invest. 110 (7): 891–8. doi:10.1172/JCI16500. PMC 151159. PMID 12370264. Unknown parameter |month= ignored (help)
  12. Schumacher D, Tischer B, Trapp S, Osterrieder N (2005). "The protein encoded by the US3 orthologue of Marek's disease virus is required for efficient de-envelopment of perinuclear virions and involved in actin stress fiber breakdown". J Virol. 79 (7): 3987–97. PMID 15767401.
  13. Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH (2003). "Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1". Nat Immunol. 4 (4): 321–9. doi:10.1038/ni907. PMID 12612580. Unknown parameter |month= ignored (help)
  14. Kusumi I, Masui T, Kakiuchi C, Suzuki K, Akimoto T, Hashimoto R, Kunugi H, Kato T, Koyama T (2005). "Relationship between XBP1 genotype and personality traits assessed by TCI and NEO-FFI". Neurosci Lett. 391 (1–2): 7–10. doi:10.1016/j.neulet.2005.08.023. PMID 16154272. Unknown parameter |month= ignored (help)
  15. Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS (2008). "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease". Cell. 134 (5): 743–56. doi:10.1016/j.cell.2008.07.021. PMID 18775308. Unknown parameter |month= ignored (help)

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