The secretory pathway
What is the secretome?
Secretome is all the components that participate in the secretion of a molecule, for example a protein. 15% of proteins in human genome contribute to secretory pathway. It all begins at the endoplasmic reticulum (the port of entry for the pathway).
What does the endoplasmic reticulum (ER) do?
The endoplasmic reticulum has many roles, for example lipid synthesis, and is the site of protein synthesis. Protein translocation occurs here additionally through the translocation pore, where proteins are folded, assembled and N-glycosylated. The ER also functions in quality control, meaning if proteins fail to assemble or fold correctly, they are degraded.
How do proteins enter the secretory pathway?
Secretory proteins carry an N-terminal signal sequence (a short peptide), this makes them able to target the surface of the endoplasmic reticulum. In simpler terms, the protein has a sequence which says, ‘I am a protein that wants to go through the ER.’ The process is co-translational meaning it happens at same time the protein is made. It leads to the docking of a ribsome-nascent chain complex onto the ER membrane. Once the protein is in the ER, the signal sequence is removed.
The next stop in the secretory pathway is the Golgi Complex.
The Golgi complex consists of the Golgi apparatus (a system of fluid filled membrane sacs) and the Golgi vesicles (used to transport substances modified at the Golgi apparatus.) Here at the Golgi complex protein and lipid modification takes place, this involves Glycan processing and Tyrosine sulfation. Molecules are packaged and sorted (to the outside, to the plasma membrane, to lysosomes.)
A key thing to remember is that the lumen of the secretory pathway is topologically equivalent to the outside of the cell.
What are transport Vesicles
These bud from a donor compartment and fuse with an acceptor compartment allowing transport. Whilst this takes place the topology of the membrane is preserved. When proteins are actually in the Endoplasmic reticulum travelling towards the plasma membrane for secretion, they do not need signals for their sorting therefore they are secreted by default. But substances that are not made to be secreted (e.g lysosomes) as they have designated destinations within the cell, must have a sorting signal in order for them to be separated from proteins with extracellular destinations. A lot of enzymes will have an intracellular destination and so must be sorted correctly, ending up in the correct vesicles for transport.
What are lysosomes?
Lysosomes are a type of enzyme that have the purpose of degrading substances, whether that be invading cells, old cells or bacteria. They have digestive properties making them highly useful. They are the intracellular endpoint of the secretory pathway and can be considered the molecular dustbins of the animal cell. They operate at low pH and are rich in hydrolytic enzymes. There are several different types of lysosomes for different molecules, you may be familiar with some. For example proteases, nucleases, glucosidases, and lipases. All lysosomal enzymes are glycoproteins meaning they contain glycan (sugar.)
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