ATP release through lysosomal exocytosis from peripheral nerves: the effect of lysosomal exocytosis on peripheral nerve degeneration and regeneration after nerve injury.

Junyang Jung,Hyun Woo Jo,Hyunseob Kwon,Na Young Jeong

doi:10.1155/2014/936891

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.

Highlights

Lysosomes are acidified, enzyme-containing intracellular organelles that break down phagocytosed materials, cell debris, and waste materials [1]
The current belief is that lysosomal exocytosis is involved in Schwann cell demyelination, remyelination, dedifferentiation, and proliferation during Wallerian degeneration
In the peripheral nervous system (PNS), an important role for lysosomal exocytosis is that it releases adenosine 5󸀠triphosphate (ATP) from peripheral neurons and Schwann cells

Summary

Introduction

Enzyme-containing intracellular organelles that break down phagocytosed materials, cell debris, and waste materials [1]. It was recently demonstrated that lysosomes play an additional role in regulating exocytosis (secretory lysosomes) in addition to degrading old materials [4]: regulated secretion. This mature lysosome exocytic process can be triggered following an increase in the free Ca2+ concentration above 1 μM. Contrary to a previous study [24], recently, it was reported that ATP release from microglia is dependent on the exocytosis via a vesicular nucleotide transporter (VNUT) but not lysosomal vesicles [25]. In this review, we discuss the dynamics of ATP related to lysosomal exocytosis in the PNS and the role of lysosomal exocytosis during Wallerian degeneration (Figure 1)

ATP Release through Lysosomal Exocytosis in the PNS

Lysosomal Exocytosis and Schwann Cell Demyelination

Lysosomal Exocytosis and Schwann Cell Dedifferentiation and Proliferation

Concluding Remarks