Lysosomal Exocytosis: The Extracellular Role of an Intracellular Organelle

Abstract

Lysosomes are acidic cell compartments containing a large set of hydrolytic enzymes. These lysosomal hydrolases degrade proteins, lipids, polysaccharides, and nucleic acids into their constituents. Materials to be degraded can reach lysosomes either from inside the cell, by autophagy, or from outside the cell, by different forms of endocytosis. In addition to their degradative functions, lysosomes are also able to extracellularly release their contents by lysosomal exocytosis. These organelles move from the perinuclear region along microtubules towards the proximity of the plasma membrane, then the lysosomal and plasma membrane fuse together via a Ca2+-dependent process. The fusion of the lysosomal membrane with plasma membrane plays an important role in plasma membrane repair, while the secretion of lysosomal content is relevant for the remodelling of extracellular matrix and release of functional substrates. Lysosomal storage disorders (LSDs) and age-related neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases, share as a pathological feature the accumulation of undigested material within organelles of the endolysosomal system. Recent studies suggest that lysosomal exocytosis stimulation may have beneficial effects on the accumulation of these unprocessed aggregates, leading to their extracellular elimination. However, many details of the molecular machinery required for lysosomal exocytosis are only beginning to be unravelled. Here, we are going to review the current literature on molecular mechanisms and biological functions underlying lysosomal exocytosis, to shed light on the potential of lysosomal exocytosis stimulation as a therapeutic approach.

The activities of LRRK2 and GCase are positively correlated in clinical biospecimens and experimental models of Parkinson’s disease

“…It has been previously reported that lysosomal enzyme activity can be measured in the plasma of patients 32 , suggesting that these proteins are likely to be secreted in certain conditions. In particular, this may occur via lysosomal exocytosis, which is a Ca 2+ -regulated process important for plasma membrane repair and secretion 33 . This may be relevant and deserves further investigation to understand if LRRK2 is involved in the regulation of the pathway and to evaluate if GCase measurement in the plasma (together or alternatively to PBMCs) could be used as a biomarker at least for certain PD forms and may allow patient stratification.…”

Collective Regulation of Metabolism, Development and Longevity Through a Socially Exchanged Fluid

“…Lysosomal pathways are enriched in our set of significantly varying trophallactic fluid proteins according to the KEGG analysis. Lysosomes are clearly acidic and can be major players in secretion, autophagic flux and exocytosis (Csizmadia et al, 2018;Maruzs et al, 2019;Tancini et al, 2020). The lysosomal signatures we see in trophallactic fluid may be traces of the mechanism of secretion, or perhaps be evidence of how this fluid has evolved.…”

Differential proteomic analysis of laser-microdissected penetration glands of avian schistosome cercariae with a focus on proteins involved in host invasion

“…The same can actually be applied to the prolyl and thimet oligopeptidases, leucyl aminopeptidase, and the PAg-exclusive serine carboxypeptidase cathepsin A. These are ubiquitous in cells of eukaryotes where they make up a constitutive peptidolytic equipment participating in, e.g., degradation of peptides generated by proteasomes, peptide catabolism in digestive cells, and are frequently mentioned in context with the catabolism of bioactive peptides such as bradykinin, angiotensin, substance P, and endothelin 1 (e.g., Saric et al, 2004;Timur et al, 2016;Fülöp et al, 2020). This implies the interference of schistosome cercariae with blood pressure and vasoconstriction at the site of parasite entry to the circulatory system.…”

“…To our best knowledge, there have been no studies so far performed on the qualitative composition of schistosome gland vesicles -are they varied within a particular gland type? Also, the presence of "true" lysosomes within the glands and their exocytosis have not been studied (Tancini et al 2020). Thus, besides the few examples of gland peptidases studied in the context of histolysis of host tissues, such as elastases, cathepsin B2 and leishmanolysins, uncovering the functions of many others requires further research.…”