Abstract:
:A challenging question in biology is how cells control their shape and volume. The relative abundance of organelles can be radically modified to comply with a new task, an example being the massive development of the endoplasmic reticulum (ER) in Ig-secreting plasma cells. The ER is the site where secretory proteins are made and folded. Remarkably, it can discriminate between native and non-native proteins, restricting transport to the former, whilst retaining and eventually degrading the latter (quality control). Recent studies revealed that certain components of the unfolded protein response (UPR), a multidimensional signalling pathway originally discovered in cells exposed to severe ER stress, are crucial for the normal development of secretory cells. According to the cell types, different arms of the UPR are required: the IRE1-XBP1 pathway is essential for plasma cell differentiation, whilst the PERK-eIF2alpha pathway is essential for pancreatic beta cells survival. Therefore, the UPR is far from being a monolithic response. Disturbances in the signalling pathways that allow the ER to satisfy the changing demand of protein synthesis can occur at various levels and often cause diseases. Here we summarize the molecular mechanisms underlying this variegated and constantly growing class of pathological conditions, focusing on diseases that are linked to alterations in the quality control functions that the ER exerts over its protein products.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Otsu M,Sitia Rdoi
10.2174/092986707780830952subject
Has Abstractpub_date
2007-01-01 00:00:00pages
1639-52issue
15eissn
0929-8673issn
1875-533Xjournal_volume
14pub_type
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