Endoplasmic reticulum protein targeting from

How does the cell sort and transport phospholipids from the site of synthesis to other membranes in the cell One view is that phospholipid vesicles that bud from the endoplasmic reticulum are targeted to another membrane where the vesicles fuse with the membrane. Alternatively, phospholipid transfer proteins may be involved. Proteins that transfer phospholipids between membranes in vitro have been known for over 25 years but it has not been demonstrated that they function in this way in vivo. 

A subsequent study in 2002 of 27 families with a condition known as multiminicore disease (MmD) also linked mutations in SEPNl to disease pathology. Multiple mutations were identified in exons 1, 5, 7, 8, 10, and 11, and the authors also mentioned that this region (RSMD) had been previously linked to MmD. Minicores are lesions by histochemistry of mitochondrial depletion within muscle tissue. The first biochemical study of selenoprotein N aimed to identify the protein localization by immunohistochemistry and found that the primary protein product of several identified mRNAs (splice variants) was a 70 kDa protein present in the endoplasmic reticulum. Two potential ER targeting domains were shown to be present and the peptide expressed from the first exon was shown to be required for localization into the ER. This study also revealed that selenoprotein N was an integral membrane protein that is N-glycosylated. Expression analysis showed pronounced levels in embryonic tissue with a reduction after development and differentiation. 

The path that leads from full sized protein to epitopes at the cell surface is complex, consisting of the generation of small peptides, translocation of the peptides to the endoplasmic reticulum by a transporter complex, loading of the peptides onto MHC class-I molecules and relocation of the MHC class-I-peptide complex to the cell surface (Rock and Goldberg, 1999). Since many of these steps are known to be prime targets for viral evasion strategies, the next step was to identify at what point the GAr interferes with the presentation of EBNAl. 

Both the integral membrane proteins of peroxisomes as well as the peroxisomal matrix proteins are synthesised on free polyribosomes and are specifically targeted to peroxisomes via dedicated peroxisomal targeting signals. The biogenesis of peroxisomes follows a sequential pattern, which involves first the insertion of peroxisomal membrane proteins into the membrane of the pre-peroxisomal structure, derived from the endoplasmic reticulum, followed by insertion of the various matrix proteins. 

Inositol trisphosphate, a water-soluble compound, diffuses from the plasma membrane to the endoplasmic reticulum, where it binds to specific IP3 receptors and causes Ca2+ channels within the ER to open. Sequestered Ca2+ is thus released into the cytosol (step (5)), and the cytosolic [Ca2+] rises sharply to about 10 6 m. One effect of elevated [Ca2+] is the activation of protein kinase C (PKC). Diacylglycerol cooperates with Ca2+ in activating PKC, thus also acting as a second messenger (step (6)). PKC phosphorylates Ser or Thr residues of specific target proteins, changing their catalytic activities (step (7)). There are a number of isozymes of PKC, each with a characteristic tissue distribution, target protein specificity, and role. 

Secretory proteins have an N-terminal signal peptide which targets the protein to be synthesized on the rough endoplasmic reticulum (RER). During synthesis it is translocated through the RER membrane into the lumen. Vesicles then bud off from the RER and carry the protein to the Golgi complex, where it becomes glycosylated. Other vesicles then carry it to the plasma membrane. Fusion of these transport vesicles with the plasma membrane then releases the protein to the cell exterior. 

---