Subsurface cisterna-lined axonal invaginations and double-walled vesicles at the axonal–myelin sheath interface

Li, Yanchao; Li, Yongnan; Cheng, Chang-Xie; Sakamoto, Hiroshi; Kawate, Toyoko; Shimada, Osamu; Atsumi, Saoko

doi:10.1016/j.neures.2005.07.006

Cited by 34 publications

(35 citation statements)

References 28 publications

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“…6A b and c and SI Fig. 12A) (25,26), some of them appeared to originate from axonal subsurface cisternae (27) or smooth endoplasmic reticulum (29) (Fig. 6A d and e).…”

Section: Discussionmentioning

confidence: 95%

“…Some of them appear to be continuous with the axonal plasma membrane (Fig. 6A d and e), which are enwrapping portions of axoplasm (27). The average number of these distinct doublemembrane vacuole-like structures (both closed and in the process of formation) in Purkinje cell axons of Atg7 flox/flox mice was Ϸ0.9/50 m 2 (Fig.…”

Section: Vacuole-like Structures With Double Membranes Were Formed Inmentioning

confidence: 92%

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Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration

Komatsu

Wang

Holstein

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

564

453

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Autophagy is a regulated lysosomal degradation process that involves autophagosome formation and transport. Although recent evidence indicates that basal levels of autophagy protect against neurodegeneration, the exact mechanism whereby this occurs is not known. By using conditional knockout mutant mice, we report that neuronal autophagy is particularly important for the maintenance of local homeostasis of axon terminals and protection against axonal degeneration. We show that specific ablation of an essential autophagy gene, Atg7, in Purkinje cells initially causes cell-autonomous, progressive dystrophy (manifested by axonal swellings) and degeneration of the axon terminals. Consistent with suppression of autophagy, no autophagosomes are observed in these dystrophic swellings, which is in contrast to accumulation of autophagosomes in the axonal dystrophic swellings under pathological conditions. Axonal dystrophy of mutant Purkinje cells proceeds with little sign of dendritic or spine atrophy, indicating that axon terminals are much more vulnerable to autophagy impairment than dendrites. This early pathological event in the axons is followed by cell-autonomous Purkinje cell death and mouse behavioral deficits. Furthermore, ultrastructural analyses of mutant Purkinje cells reveal an accumulation of aberrant membrane structures in the axonal dystrophic swellings. Finally, we observe double-membrane vacuole-like structures in wild-type Purkinje cell axons, whereas these structures are abolished in mutant Purkinje cell axons. Thus, we conclude that the autophagy protein Atg7 is required for membrane trafficking and turnover in the axons. Our study implicates impairment of axonal autophagy as a possible mechanism for axonopathy associated with neurodegeneration.axon ͉ axonopathy ͉ neurodegeneration ͉ autophagosome ͉ Purkinje cell M acroautophagy is characterized by dynamic membrane rearrangements, involving the formation, trafficking, and degradation of double-membrane autophagic vacuoles (autophagosomes) in the cytoplasm. Macroautophagy (hereafter referred to as autophagy) is a highly regulated process, which can be induced by nutrient starvation, trophic factors, and stress (1). Despite recent advances in characterizing autophagy in several model systems, autophagic processes in the nervous system remain poorly understood. On one hand, nutrient deprivation has not been observed to induce autophagy in the mammalian brain (2), thus suggesting a specific regulatory system for autophagy that is not typically activated by starvation. On the other hand, a variety of conditions that cause neuronal stress or degeneration can lead to the accumulation of autophagosomes in neurons, thus implicating autophagy in these neuropathogenic processes (3, 4).The axon is a highly specialized neuronal compartment that performs many functions independently from the cell body. After axotomy or excitotoxicity, double-membrane vacuoles resembling autophagosomes were originally observed to accumulate in dilated axon terminals that result fro...

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“…6A b and c and SI Fig. 12A) (25,26), some of them appeared to originate from axonal subsurface cisternae (27) or smooth endoplasmic reticulum (29) (Fig. 6A d and e).…”

Section: Discussionmentioning

confidence: 95%

Section: Vacuole-like Structures With Double Membranes Were Formed Inmentioning

confidence: 92%

Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration

Komatsu

Wang

Holstein

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

564

453

View full text Add to dashboard Cite

show abstract

“…Some of these vesicles are continuous with the subjacent axon. They are thought to be involved in the transfer of glial ribosomes to the axon (206). Comparable ultrastructural data have recently been reported in the rat sciatic nerves examined with an antiribosomal polyclonal antibody (195).…”

Section: B Vertebrate Axonsmentioning

confidence: 87%

Local Gene Expression in Axons and Nerve Endings: The Glia-Neuron Unit

Giuditta¹,

Chun²,

Eyman³

et al. 2008

Physiological Reviews

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Neurons have complex and often extensively elongated processes. This unique cell morphology raises the problem of how remote neuronal territories are replenished with proteins. For a long time, axonal and presynaptic proteins were thought to be exclusively synthesized in the cell body, which delivered them to peripheral sites by axoplasmic transport. Despite this early belief, protein has been shown to be synthesized in axons and nerve terminals, substantially alleviating the trophic burden of the perikaryon. This observation raised the question of the cellular origin of the peripheral RNAs involved in protein synthesis. The synthesis of these RNAs was initially attributed to the neuron soma almost by default. However, experimental data and theoretical considerations support the alternative view that axonal and presynaptic RNAs are also transcribed in the flanking glial cells and transferred to the axon domain of mature neurons. Altogether, these data suggest that axons and nerve terminals are served by a distinct gene expression system largely independent of the neuron cell body. Such a local system would allow the neuron periphery to respond promptly to environmental stimuli. This view has the theoretical merit of extending to axons and nerve terminals the marginalized concept of a glial supply of RNA (and protein) to the neuron cell body. Most long-term plastic changes requiring de novo gene expression occur in these domains, notably in presynaptic endings, despite their intrinsic lack of transcriptional capacity. This review enlightens novel perspectives on the biology and pathobiology of the neuron by critically reviewing these issues.

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“…Interestingly, axons seem to receive various mRNA packed in shedding microvesicles from Schwann cells at nodes of Ranvier. By shedding microvesicles, gene expression of these glial cells seems to locally sustain protein synthesis in axons independently, at least in part [7,9,19]. Shedding of microvesicles from microglia, astrocytes, oligodendrocytes and neurons is triggered by ATP via P2X7R [28].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury

Song

Zhu

et al. 2015

Purinergic Signalling

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Peripheral nerve injury (PNI) is a common disease, which results in a partial or total loss of motor, sensory and autonomic functions, leading to a decrease in quality of life. Schwann cells play a vital role in maintaining the peripheral nervous system and in injury and repair. Using immunohistochemistry, Western blot, calcium assay and bromodeoxyuridine (BrdU) proliferation assay, the present study clearly demonstrated that P2X7 receptors (R) were expressed in myelinating and non-myelinating Schwann cells in longitudinal sections of sciatic nerves. After sciatic nerve injury (SNI), P2X7R expression in Schwann cells of injured sciatic nerves was significantly up-regulated during the early days of SNI. Double immunofluorescence of proliferating cell nuclear antigen (PCNA) and P2X7R implied that P2X7R may be involved in proliferation of Schwann cells. Further experiments on primary cultures of Schwann cells showed that P2X7R are functionally expressed in Schwann cells of rat sciatic nerves; ATP via P2X7R can promote Schwann cell proliferation, possibly via the MAPK/ERK intracellular signalling pathway. Other possible roles of P2X7R on Schwann cells are discussed.

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Subsurface cisterna-lined axonal invaginations and double-walled vesicles at the axonal–myelin sheath interface

Cited by 34 publications

References 28 publications

Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration

Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration

Local Gene Expression in Axons and Nerve Endings: The Glia-Neuron Unit

Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury

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