Abstract
Protein secretion in general depends on signal sequence (also named leader sequence), a hydrophobic segment located at or close to the NH2-terminus of a secretory or membrane protein. This sequence guides the entry of nascent polypeptides into the lumen or membranes of the endoplasmic reticulum (ER) for folding, assembly, and export. However, evidence accumulated in recent years has suggested the existence of a collection of unconventional protein secretion (UPS) mechanisms that are independent of the canonical vesicular trafficking route between the ER and the plasma membrane (PM). These UPS mechanisms export soluble proteins bearing no signal sequence. The list of UPS cargos is rapidly expanding, along with the implicated biological functions, but molecular mechanisms accountable for the secretion of leaderless proteins are still poorly defined. This review summarizes our current understanding of UPS mechanisms with an emphasis on the emerging role of endo-lysosomes in this process.
Highlights
The survival of individual cells relies on adaptation in response to environmental cues, which requires functional interplays between macromolecules secreted into cell exterior and their receptors on cell surface.The localization of secretory proteins is generally achieved by a leader sequence, often at or close to the NH2-terminus of nascent polypeptides emerging from the ribosome [1]
Accumulated evidence suggests that IL-1β secretion can occur via several routes, most of which involve vesicular intermediates such as microvesicles shed from the plasma membrane (PM), exosomes derived from late endosomes called multivesicular bodies (MVBs) [8,9,10], or, as demonstrated more recently, via secretory autophagosomes [11]
Several studies showed recently that IL-1β can be released into cell exterior by direct translocation across the PM through a pore formed by gasdermin D (GSDMD) in activated microphage that have been exposed to inflammasome activators [13,14]
Summary
The survival of individual cells relies on adaptation in response to environmental cues, which requires functional interplays between macromolecules secreted into cell exterior and their receptors on cell surface. Membrane insertion of FGF-2 oligomers is regulated by phosphorylation of tyrosine 81 by non-receptor tyrosine kinase Tec, which is associated with the inner leaflet of the PM through its pleckstrin homology (PH) domain [22] Both gasdermin D-mediated IL-1β secretion and auto-pore-mediated FGF-2 secretion belong to type I UPS, as cargos translocate directly across the PM during secretion [3]. Acb1-containing autophagosomes either directly fuse with the PM or mature into late endosomes/MVBs, followed by the release of Acb to the extracellular space This process is stimulated by nutrient deprivation and requires the GRASP protein Grh (the yeast orthologue of mammalian GRASP65 and GRASP55) [30]. This review summarizes our current understanding on the role of endo-lysosomes in this process
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
