Starting with a protein that has been inserted into the Endoplasmic reticulum (ER) membrane with the Amino (N) terminal in the ER lumen and the carboxy (C) terminal in the cytoplasm, describe the journey the protein will take until it is placed in the plasma membrane. Include any modifications that occur during the journey and where they occur. Also, always indicate where the N and C terminal are located.

Answer and Explanation:

Ribosomes are the primary structure for protein synthesis. They can be found in the rough endoplasmic reticulum or floating in the cytosol.  

Free ribosomes are not attached to any cytoplasmic structure or organelle. They synthesize proteins only for internal cell use. Other ribosomes are attached to the membrane of the endoplasmic reticulum and they are in charge of synthesizing membrane proteins or exportation proteins. Free and attached ribosomes are identical and they can alternate their location. This means that although free ribosomes are floating in the cytosol, eventually, they can get attached to the endoplasmic reticulum membrane.  

Synthesis of proteins that are destined to membrane or exportation starts in the cytoplasm with the production of a molecule portion known as a signal aminoacidic sequence. This signal sequence varies between 13 and 36 amino acids, is located in the amino extreme of the synthesizing protein, and when it reaches a certain length, it meets the signal recognizing particle. This particle joins the signal sequence of the protein and leads the synthesizing protein and associated ribosome to a specific region in the Rough endoplasmic reticulum where it continues the protein building. When they reach the membrane of the endoplasmic reticulum, the signal recognizing particle links to a receptor associated with a pore. Meanwhile, the ribosome keeps synthesizing the protein, and the enlarged polypeptidic chain goes forward the reticulum lumen through the pore. While this is happening, another enzyme cuts the signal sequence, an action that requires energy from the ATP hydrolysis. When the new protein synthesis is complete, the polypeptide is released into the reticulum lumen. Here it also happens the protein folding (which is possible by the formation of disulfide bridges of proteins are formed) and the initial stages of glycosylation (the oligosaccharide addition).  

Once membrane proteins are folded in the interior of the endoplasmic reticulum, they are packaged into vesicles and sent to the Golgi complex, where it occurs the final association of carbohydrates with proteins. The Golgi complex sends proteins to their different destinies. Proteins destined to a certain place are packaged all together in the same vesicle and sent to the target organelle. In the case of membrane proteins, they are packaged in vesicles and sent to the cell membrane where they get incrusted.  

There are certain signal sequences in the carboxy-terminal extreme of the protein that plays an important role during the transport of membrane proteins. A signal as simple as one amino acid in the c-terminal extreme is responsible for the correct transport of the molecule through the whole traject until it reaches the membrane.