Question

Describe, in detail, the processes involved in the synthesis and import of secretory proteins in the rough ER.

Answer 1

Rough ER - the cytosolic surface of the membranes have attached ribosomes that are synthesizing proteins for import into the ER. This is site of synthesis for proteins destined for secretion, lysosomes, or membranes

As a ribosome begins to translate mRNA, in some instances a signal sequence is initially produced resulting in the mRNA/ribosome complex being directed to endoplasmic reticulum, forming RER. The resultant protein produced by this complex is inserted into the lumen of the endoplasmic reticulum to be packaged and processed for transport to the Golgi apparatus.

Cells that produce large amounts of secretory protein contain abundant RER.

Secretory proteins are efficiently stored at high concentrations in zymogen granules by steps that sequentially enrich the proteins several hundred-fold over that found in the ER lumen ( They are also segregated away from other soluble proteins, most notably lysosomal enzymes, as they move to their final storage site.) The first step in the concentration process takes place as nascent secretory proteins are preparing to be transported in vesicles from the ER. These vesicles emerge from distinct protrusions from the RER, known as transitional elements, that are devoid of ribosomes and are close to the Golgi complex. After budding, the small vesicles with their nascent protein cargo move to an intermediate compartment known as the vesicular-tubular complex (VTC). Proteins are then transferred from the VTC to the Golgi complex by direct fusion or by vesicles that bud from the VTC.

Movement of nascent proteins from the ER is mediated by the addition of the COPII coatamer protein complex to the cytoplasmic side of the ER membrane. The COPII coat proteins are required for cargo selection, vesicle budding from the ER, and forward trafficking. The coat is sequentially assembled with the addition of the small GTPase, Sar1, followed by the soluble complexes of Sec23/24 and Sec13/31. Accessory proteins may function as a scaffold for assembly and regulate the GTPase activity of Sar1.