ATP Release through Lysosomal Exocytosis from Peripheral Nerves: The Effect of Lysosomal Exocytosis on Peripheral Nerve Degeneration and Regeneration after Nerve Injury

Abstract

Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5′-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome.

An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration

“…The involvement of ATP in peripheral (including enteric) nerve degeneration and regeneration has also been studied (see Tokui et al, 1994;Sch€ afer et al, 1995;Xu et al, 2013;Jung et al, 2014), but will not be covered in this review article, which is focussed on the CNS.…”

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

“…Astrocytes then respond to microglialderived ATP via P2Y1 receptors to trigger neuroprotection through secretion of interleukin-6 [74]. It has been shown that the microglial ATP is stored in secretory lysosomes and exocytosed upon stimulation [116]. This released ATP may act as an autocrine or paracrine messenger and trigger ATP secretion, resulting in stimulation of cell migration.…”

“…This released ATP may act as an autocrine or paracrine messenger and trigger ATP secretion, resulting in stimulation of cell migration. This may provide a positive feedback mechanism to ensure migration and accumulation of microglia towards the site of injury [69,116]. In the microglia of VNUT −/− mice, neither vesicular ATP release nor ATP-dependent secondary responses are observed [75].…”

“…Type II taste cells receive sweet, bitter, and umami tastes by way of the corresponding specific receptors and transduce taste information to the gustatory nerves by ATP signaling [127,128]. Recent work has concluded that type II taste cells secrete ATP through CALHM1 plasma membrane ATP-permeable ion channels [129].…”

Cystatin C in aging and in Alzheimer’s disease

“…In degenerating neurons, it has been suggested that cathepsins can be released directly into the cytoplasm after the disruption of lysosomes, with detrimental consequences for the cell (Bidere et al, 2003; Boland and Campbell, 2004; Kagedal et al, 2001; Roberg and Ollinger, 1998). In addition to their intracellular localization, cathepsins may be released outside of a cell through leakage from the endosomal-lysosomal system [reviewed in (Aits and Jaattela, 2013; Pislar and Kos, 2014)] and lysosomal exocytosis [reviewed in (Andrews, 2000; Blott and Griffiths, 2002; Jung et al, 2014; Sundler, 1997)]. In the brain, activated microglia secrete several proteases including Cat B (Buck et al, 1992).…”