Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function

Abstract

The endolysosomal system is present in all cell types. Within these cells, it performs a series of essential roles, such as trafficking and sorting of membrane cargo, intracellular signaling, control of metabolism and degradation. A specific compartment within central neurons, called the presynapse, mediates inter-neuronal communication via the fusion of neurotransmitter-containing synaptic vesicles (SVs). The localized recycling of SVs and their organization into functional pools is widely assumed to be a discrete mechanism, that only intersects with the endolysosomal system at specific points. However, evidence is emerging that molecules essential for endolysosomal function also have key roles within the SV life cycle, suggesting that they form a continuum rather than being isolated processes. In this review, we summarize the evidence for key endolysosomal molecules in SV recycling and propose an alternative model for membrane trafficking at the presynapse. This includes the hypotheses that endolysosomal intermediates represent specific functional SV pools, that sorting of cargo to SVs is mediated via the endolysosomal system and that manipulation of this process can result in both plastic changes to neurotransmitter release and pathophysiology via neurodegeneration.

The Epithelial Na+Channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components from old to new boutons in remodeling neurons

“…A mechanism for distal recycling of presynaptic components would likely require a transport system involving intracellular vesicles or endosomes (Ivanova & Cousin, 2022). Rab11 is a small GTPase required for recycling endosome function (Ullrich et al, 1996).…”

“…Our finding of abundant endocytic structures in remodeling DD axons and their dependence on UNC-8 which promotes presynaptic disassembly, suggested that SV components could be recycled by an ADBE-like mechanism for reassembly, in this case, to nascent presynaptic domains in dorsal DD neurites (Figure 1A) (Park et al, 2011). A mechanism for distal recycling of presynaptic components would likely require a transport system involving intracellular vesicles or endosomes (Ivanova & Cousin, 2022). Rab11 is a small GTPase required for recycling endosome function (Ullrich et al, 1996).…”

Neuronal-Immune Cell Units in Allergic Inflammation in the Nose

“…Consequently, the immune system represents the third counterpart of the combined neuroimmune system. [20] "Neurogenic" inflammation [18,21] Neuroendocrine Hypothalamus, pituitary gland, and peripheral endocrine glands (i.e., HPA axis on the whole) Endocrine gland cells NEC [11,22,23] General adaptation syndrome [16] Immune Primary, secondary, and tertiary organs Immune cells (lymphocytes and non-lymphoid immune cells) Immune cell-derived extracellular vesicles [24] Barrier epithelium's cells (ciliated, deuterosomal, goblet, club, basal, suprabasal, tuft cells, ionocytes, etc. [7,10] Innate immunity Pathways of adaptive immune responses Immune (allergen) tolerance [25,26]…”

Effects of the clathrin inhibitor Pitstop-2 on synaptic vesicle recycling at a central synapse in vivo

“…Local SV recycling at the presynapse is an essential process for the maintenance of neurotransmission ( Ceccarelli et al, 1973 ; Heuser and Reese, 1973 ). However, the exact molecular mechanisms underlying SV recycling are still not completely understood, especially in vivo (for review see Kokotos and Cousin, 2015 ; Watanabe and Boucrot, 2017 ; Chanaday et al, 2019 ; Ivanova and Cousin, 2022 ). Till date, four different, mutually non-exclusive mechanisms for synaptic endocytosis have been described.…”