Abstract
The endoplasmic reticulum (ER) supports many cellular processes and performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, and posttranslational modifications including N-linked glycosylation; and regulation of Ca2+ homeostasis. In mammalian systems, the majority of proteins synthesized by the rough ER have N-linked glycans critical for protein maturation. The N-linked glycan is used as a quality control signal in the secretory protein pathway. A series of chaperones, folding enzymes, glucosidases, and carbohydrate transferases support glycoprotein synthesis and processing. Perturbation of ER-associated functions such as disturbed ER glycoprotein quality control, protein glycosylation and protein folding results in activation of an ER stress coping response. Collectively this ER stress coping response is termed the unfolded protein response (UPR), and occurs through the activation of complex cytoplasmic and nuclear signaling pathways. Cellular and ER homeostasis depends on balanced activity of the ER protein folding, quality control, and degradation pathways; as well as management of the ER stress coping response.
Highlights
The endoplasmic reticulum (ER) is a multifunctional network of intracellular membranes responsible for the secretory protein demands of the cell as well as adaptive responses to stress
Accumulation of mis-folded proteins in the ER due to cellular insults, impaired ER homeostasis and/or disrupted glycoprotein quality control leads to activation of a specific
When the third glucose residue is removed by glucosidase II, allowing its release from the calnexin and calreticulin protein quality control cycle [1,33], the native glycoprotein is released from the ER and transits through the secretory pathway
Summary
The endoplasmic reticulum (ER) is a multifunctional network of intracellular membranes responsible for the secretory protein demands of the cell as well as adaptive responses to stress. Proteins within the ER are responsible for controlling the translation, folding, and translocation of nascent polypeptides for Molecules 2015, 20 secretion or insertion into the membrane as transmembrane proteins. The molecular chaperones of the ER are important for regulating intracellular Ca2+ signaling within the ER lumen and the rest of the cell [2,3,4]. The UPR results in ER to nucleus and ER to plasma membrane signaling, with activation of genes encoding ER chaperone expression [6], inhibition of protein synthesis and increased protein degradation [5,6]. The ER may be defined as a versatile component of the intracellular reticular network able to detect and integrate incoming signals, modulate and respond to its own luminal dynamics and generate output signals in response to environmental changes [4,5,7]
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