Omar Bennett
The secretory pathway is a critical index of a cell's capacity to incorporate proteins into cellular membranes and secrete them into the extracellular space. There are two types of secretory pathways: the regulated secretory pathway and the constitutive secretory pathway. In the regulated pathway, proteins are packaged into vesicles and stored in the cell until they are secreted in response to a specific signal. In the constitutive pathway, vesicles are continuously formed and carry proteins from the Golgi to the cell surface, where they are released in small quantities at a constant rate. This is also called the default secretory pathway, as it requires no specific signal for cargo to enter.
| Characteristics | Values |
|---|---|
| Type of secretion | Constitutive secretion |
| Other names | Default secretion, constitutive exocytic pathway |
| Requires signal for cargo to enter the pathway | No |
| Requires a specific signal for cargo to be secreted | No |
| Rate of transport | Relatively constant |
| Requires protein synthesis | No |
| Examples | Mucus from intestinal epithelial cells, Interleukins from certain white blood cells, Collagen and Proteoglycans from Fibroblasts |
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What You'll Learn
The constitutive secretion of glycosaminoglycan chains
Glycosaminoglycans (GAGs) are negatively charged polysaccharide compounds composed of repeating disaccharide units that are present in every mammalian tissue. They play a crucial role in the cell signalling process, including the regulation of cell growth, proliferation, promotion of cell adhesion, anticoagulation, and wound repair.
The constitutive secretion of GAGs remains unhindered in the absence of protein synthesis. This is in contrast to the regulated secretory pathway, where cycloheximide treatment severely impairs the cell's ability to store and secrete GAG chains. The differential requirements for protein synthesis indicate differences in the mechanisms for sorting and/or transport of molecules through the constitutive and regulated secretory pathways.
In the constitutive secretory pathway, vesicles continuously form and carry proteins from the Golgi to the cell surface. This process is also known as the default secretory pathway, as it requires no special targeting sequence beyond the ER insertion sequence required to enter the endomembrane system. Once the secretory vesicle reaches the cell membrane, it fuses with the surface membrane, releasing its cargo into the extracellular space.
The constitutive secretion of GAG chains is an example of how the constitutive secretory pathway operates. This pathway does not require components supplied by new protein synthesis, as secretion is not affected by cycloheximide. The constitutive secretion of GAG chains is important for the proper functioning of cells and the maintenance of bodily functions.
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Constitutive secretion vs regulated secretion
The secretory pathway carries proteins to the cell surface membrane where they can be released. This process can be divided into two systems: the regulated secretory pathway and the constitutive secretory pathway.
Regulated Secretion
The regulated secretory pathway operates by creating a storage compartment within cells to store secretory cargo. These storage compartments can fuse with the cell surface and allow a burst of contents to be rapidly secreted upon receiving the appropriate stimulus. This type of release is called regulated secretion. An example of regulated secretion is the release of gastrointestinal hormones and digestive enzymes in response to the ingestion of food.
Constitutive Secretion
In the constitutive secretory pathway, vesicles continuously form and carry proteins from the Golgi to the cell surface. This is also sometimes called the default secretory pathway, as it requires no special targeting sequence beyond the ER insertion sequence required to first enter the endomembrane system for cargo to get secreted via this pathway. For many proteins in the constitutive secretory pathway, this transport process occurs at a relatively constant rate that is determined by how quickly those proteins are synthesized. An example of constitutive secretion is the secretion of mucus from intestinal epithelial cells.
Molecules That Undergo Constitutive Secretion
Certain white blood cells constitutively secrete specific interleukins, which are signalling molecules that play an important role in the function of the immune system. Cells such as fibroblasts also constitutively secrete proteins like collagen and proteoglycans into the extracellular matrix.
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The role of vesicles in constitutive secretion
The constitutive secretion pathway is a critical process that exists in all cells, and it is characterised by the absence of specific signals for cargo to enter this pathway. This pathway is responsible for the continuous secretion of soluble proteins and other substances from the cell.
The Golgi apparatus, located near the cell's ribosomes and endoplasmic reticulum (ER), is responsible for sorting and packaging proteins into vesicles. These vesicles then travel to the cell surface, where they fuse with the plasma membrane through a process called exocytosis. The fusion of the vesicles with the plasma membrane results in the release of their soluble protein cargo into the extracellular space. This release occurs in a relatively constant manner, determined by the rate of protein synthesis.
Lipids, especially cholesterol, play a crucial role in vesicle formation during constitutive secretion. The presence of specific lipids, such as phosphatidic acid (PA) and cholesterol, is necessary for vesicle budding at the trans-Golgi network (TGN). Additionally, proteins like GTPases and dynamin are involved in vesicle budding and release. GTPases cycle between active and inactive forms, contributing to membrane fission and vesicle release. Dynamin, in the presence of GTP, forms assemblies that drive vesicle release.
In summary, vesicles are integral to the process of constitutive secretion. They facilitate the transport of proteins from the Golgi apparatus to the cell surface, where the vesicles fuse with the plasma membrane, releasing their protein cargo through exocytosis. This continuous process is a vital mechanism for cells to secrete proteins and maintain their function.
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The default secretion pathway
The constitutive secretion pathway is one of two main types of secretory pathways, the other being the regulated secretion pathway. In the regulated pathway, molecules are packaged into vesicles and stored within the cell until a specific signal triggers their release. This allows for controlled bursts of secretion in response to stimuli. In contrast, the constitutive pathway does not rely on specific signals or storage compartments. Instead, vesicles continuously form and carry molecules from the Golgi to the cell surface, where they fuse with the plasma membrane and immediately release their cargo. This process occurs at a relatively constant rate determined by the synthesis rate of the molecules being transported.
The constitutive secretion pathway is particularly important for certain types of cells and molecules. For example, certain white blood cells use this pathway to secrete specific interleukins, which are signalling molecules that play a crucial role in intercellular communication and immune system function. Additionally, cells like fibroblasts constitutively secrete proteins such as collagen and proteoglycans into the extracellular matrix, contributing to essential structural and functional roles.
At a molecular level, the constitutive secretion pathway involves several key steps. Molecules destined for secretion via this pathway are co-translationally translocated into the lumen of the endoplasmic reticulum (ER). Once inside the ER, they proceed to ER exit sites (ERES) where they are incorporated into membrane-coating COPII vesicles. These vesicles then transport the molecules to the ER-to-Golgi intermediate compartment (ERGIC) before being routed to the Golgi apparatus. After passing through the Golgi stacks, molecules undergo further processing and maturation. At the trans-Golgi network (TGN), they are sorted into different vesicles or carriers for trafficking to their final destinations, including the plasma membrane or cell surface.
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Constitutive secretion in neural and endocrine cells
Many neural and endocrine cells possess two pathways of secretion: a regulated pathway and a constitutive pathway. The regulated pathway facilitates the specialized function of excitable cells such as neurons and endocrine cells, which is to synthesize, store, and secrete on-demand hormones, neuropeptides, and neurotransmitters. In the regulated pathway, proteins are packaged into vesicles that are stored in the cell until they are secreted in response to a specific signal. For example, vesicles containing insulin build up in the cell until a glucose signal enters the cell, initiating a complicated process that leads to the release of insulin.
On the other hand, the constitutive pathway predominantly facilitates housekeeping functions, including protein insertion into the plasma membrane, secretion of extracellular matrix components, growth hormones, and plasma proteins. In this pathway, vesicles continuously form and carry proteins from the Golgi to the cell surface. This is also called the default pathway, as it requires no specific signal for cargo to enter and be secreted. For many proteins in the constitutive pathway, the transport process occurs at a relatively constant rate determined by how quickly the proteins are synthesized.
The secretory pathway is critical for a cell's capacity to incorporate proteins into cellular membranes and secrete proteins into the extracellular space. Intracellular protein trafficking and sorting are particularly challenging in endocrine and neuroendocrine cells, which synthesize and secrete substantial quantities of proteins on demand. To ensure that neuroendocrine secretion operates correctly, each step in the secretion pathways is tightly regulated and coordinated both spatially and temporally.
Constitutive secretion is not affected by cycloheximide, suggesting that the operation of this pathway does not require components supplied by new protein synthesis.
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Frequently asked questions
Constitutive secretion is a form of secretion that occurs continuously and is independent of any specific signal or stimulus. It is also known as the default pathway as it does not require any specific targeting sequence for cargo to enter.
Molecules that undergo constitutive secretion include certain proteins, such as collagen and proteoglycans, which are secreted by cells like fibroblasts. Intestinal epithelial cells also secrete mucus through constitutive secretion. Additionally, neural and endocrine cells can release surface-bound proteins via this pathway.
Regulated secretion involves storing proteins or molecules in vesicles within the cell until a specific signal or stimulus triggers their release. This type of secretion is used for tasks like hormonal control and neuronal communication. Constitutive secretion, on the other hand, does not involve storing cargo and releases molecules directly from the cell.
An example of constitutive secretion is the release of specific Interleukins, which are signaling molecules, from certain white blood cells. This plays a crucial role in intercellular communication and immune system function.
