Constitutive versus regulatory secretory pathways
Cells release proteins by two main secretory routes: the constitutive route sends them out continuously without storage, whereas the regulatory route stores them in vesicles until a signal arrives.
Remember
Proteins needed all the time, such as collagen, albumin and antibodies, are released continuously, whereas stored products such as insulin are released only when a signal arrives.
Proteins that leave a cell by the usual secretory route are made on the endoplasmic reticulum (a folded network of membrane), sorted in the Golgi apparatus (the cell's sorting and packing station) and packed into vesicles (small membrane bubbles).
In the constitutive secretory pathway, vesicles go straight to the plasma membrane (the outer boundary of the cell) and fuse with it, so the protein leaves continuously, with no storage step and no trigger needed. Collagen, albumin and antibodies leave this way. Fibroblasts, for example, secrete procollagen (the form in which collagen leaves the cell) all the time, because connective tissue is constantly being built.
In the regulatory secretory pathway (also called the regulated pathway), the protein is held in storage vesicles until a stimulus (a signal) arrives. For example, a hormone or neurotransmitter binding to a receptor on the cell surface starts signalling inside the cell, and only then do the stored vesicles fuse with the membrane and release their contents by exocytosis (a vesicle fusing with the membrane and tipping its contents outside). Insulin, ACTH (adrenocorticotropic hormone) and trypsinogen (the inactive precursor of trypsin, a protein-digesting enzyme) are released this way.
Insulin is a classic stored hormone. It waits in secretory granules (storage vesicles) inside pancreatic beta cells (the cells of the pancreas that make and store insulin), and a stimulus such as a rise in blood glucose triggers its release. The connecting peptide (C-peptide, the piece cut away when insulin is made) is stored in the same granules and leaves the cell together with insulin.
Both pathways share the early steps: each starts with a signal peptide (a short address label) and passes through the endoplasmic reticulum, the Golgi apparatus and vesicles, and each ends in exocytosis.
Key facts
- Constitutive pathway
- vesicles fuse with the plasma membrane straight away, so release is continuous, with no storage and no trigger.
- Regulatory pathway
- the protein is stored in vesicles and released only after a signal, such as a hormone or neurotransmitter binding to a receptor on the cell surface.
- Constitutive examples
- collagen, albumin and antibodies are proteins needed all the time.
- Regulatory examples
- insulin, ACTH and trypsinogen (the inactive precursor of trypsin).
- Shared steps
- both pathways start with a signal peptide and pass through the endoplasmic reticulum, the Golgi apparatus and vesicles.
- Insulin trigger
- stored insulin is released mainly when blood glucose rises.
Exam traps
- A stored hormone such as insulin does not leave by the constitutive pathway, because that pathway has no storage and no trigger, whereas insulin is held in secretory granules until a stimulus such as a rise in blood glucose.
- Albumin does not take the regulatory pathway: liver cells release it into the blood continuously rather than storing it, so it is a constitutive protein like collagen.
- Bypassing the Golgi apparatus does not separate the two pathways, because both run through the endoplasmic reticulum and the Golgi apparatus before the vesicles are sorted.
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