positive regulation of secretion of lysosomal enzymes

Definition

Target type: biologicalprocess

Any process that increases the rate, frequency or extent of secretion of lysosomal enzymes, the controlled release of lysosomal enzymes by a cell. [GOC:BHF]

Positive regulation of secretion of lysosomal enzymes is a complex process involving multiple cellular mechanisms and signaling pathways. It plays a crucial role in various physiological functions, including cellular degradation, antigen presentation, and extracellular matrix remodeling.

The process begins with the synthesis and sorting of lysosomal enzymes within the endoplasmic reticulum (ER). Newly synthesized lysosomal enzymes are tagged with mannose-6-phosphate (M6P) residues, which act as recognition signals for their packaging into lysosomes.

The M6P-tagged enzymes then travel to the Golgi apparatus where they are sorted into clathrin-coated vesicles. These vesicles bud off from the trans-Golgi network and fuse with late endosomes.

Within late endosomes, the pH is acidic, which triggers the release of M6P receptors. The lysosomal enzymes dissociate from the receptors and are transported to lysosomes.

However, in certain situations, lysosomal enzymes can be secreted out of the cell. This process, known as lysosomal exocytosis, can be regulated by various factors, including:

* **Cytokine signaling:** Cytokines like TNF-α and IL-1β can induce the secretion of lysosomal enzymes.
* **Cellular stress:** Stress conditions, such as oxidative stress or hypoxia, can trigger the release of lysosomal enzymes.
* **pH changes:** Alterations in intracellular pH can modulate the activity of lysosomal enzymes and influence their secretion.
* **Calcium signaling:** Calcium ions can activate specific kinases and phosphatases that regulate the trafficking and secretion of lysosomal enzymes.
* **Lipid signaling:** Lipid mediators, such as phosphoinositides and ceramide, can influence the formation of secretory vesicles and the release of lysosomal enzymes.

The specific mechanisms by which these factors regulate lysosomal enzyme secretion are still under investigation. However, it is believed that they converge on pathways that control the formation and fusion of secretory vesicles with the plasma membrane.

The positive regulation of lysosomal enzyme secretion is tightly controlled to ensure that these powerful hydrolytic enzymes are released only when needed. Dysregulation of this process can contribute to various diseases, including lysosomal storage disorders and autoimmune disorders.'
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