Secretory pathway

The secretory pathway is a series of steps a cell uses to move proteins out of the cell; a process known as secretion. The path of a protein destined for secretion has its origins in the rough endoplasmic reticulum, a membrane-bound compartment in the cell. The protein then proceeds through the many compartments of the Golgi apparatus and finally ends up in a vesicle that fuses with the plasma membrane, dumping the proteins outside of the cell. At each step along the way there are crucial factors that determine how and if the protein will proceed. Some of these factors include regulation of transportation, selection of particular proteins, the mechanics of proceeding to the next step, and modifications that can occur to the protein along the way. All of these factors contribute to how a protein arrives outside of a cell after being synthesized.

General Regulation
In general, there are two different patterns of secretion. One pattern is called constitutive secretion. Proteins are continuously secreted from the cell regardless of environmental factors. No external signals are needed to initiate this process. Proteins are packaged in vesicles in the Golgi apparatus and are secreted via exocytosis, all around the cell. Cells that secrete constitutively have Golgi apparatus scattered throughout the cytoplasm. Fibroblasts, osteoblasts and chondrocytes are some of the many cells that perform constitutive secretion.

In regulated secretion, proteins are packaged as described in the constitutive pathway, but they are only secreted in response to a specific signal, such as neural or hormonal stimulation. Cells that use the regulated secretory pathway are usually apical or polarized, meaning that they secrete multiple classes of proteins. The Golgi apparatus is found in a supranuclear position (between the nucleus and the secretory surface). Examples of cells that use regulated pathway are: goblet cells (secrete mucus), beta cells of the pancreas (secrete insulin) and odontoblasts (secrete dentin). The protein pathway consists of eight steps total.

Protein Translocation
The first step in a protein's journey out of the cell is getting into the endoplasmic reticulum. Two methods exist for proteins to accomplish this. One is co-translational translocation and the other is post-translational translocation.


 * Co-Translational translocation is the action of a protein being fed into the ER as it is synthesized by the ribosome. In this scenario the protein begins to be translated normally.  As the N-terminus (the first end of the protein to be synthesized) leaves the ribosome, a short sequence of the nascent protein's amino acids is recognized by a protein complex called SRP, or signal recognition particle.  SRP binds to this sequence of amino acids and then subsequently binds to a protein complex called the SRP receptor embedded in the ER membrane.  Both the SRP complex and SRP receptor complex hydrolyze a molecule of GTP into GDP.  Once this occurs the growing protein chain is moved to a membrane channel called the translocon.  It is through this hole in the ER membrane that the protein passes through as it is synthesized.  The result of all this is a new protein residing within the membrane of the endoplasmic reticulum.


 * Post-Translational translocation is the action of a protein passing into the ER following synthesis by the ribosome.