The Role of Vesicle Trafficking and Release in Oligodendrocyte Biology

Reiter, Cory R.; Bongarzone, Ernesto R.

doi:10.1007/s11064-019-02913-2

Cited by 15 publications

(11 citation statements)

References 99 publications

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“…Within the nervous system, vesicle-dependent signaling is important for myelin formation as well as trafficking within the myelin sheath (Baron and Hoekstra, 2010;Reiter and Bongarzone, 2020;White and Krämer-Albers, 2014). Electron micrographs show that CD59a is positioned throughout the myelin sheath in oligodendrocytes (Siems et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Beyond complement-inhibitory functions, Cd59 can also facilitate vesicle signaling in insulin-producing pancreatic cells (Golec et al, 2019;Krus et al, 2014), suppress cell proliferation in T cells responding to a viral infection (Longhi et al, 2005) or smooth muscle cells in models of atherosclerosis (Li et al, 2013), and orchestrate proximal-distal cell identity during limb regeneration (Echeverri and Tanaka, 2005). Like complementinhibition, these processes are critical to normal nervous system function (Almeida et al, 2021;Baron and Hoekstra, 2010;Reiter and Bongarzone, 2020;White and Krämer-Albers, 2014). However, it is unclear exactly what role Cd59 is playing in myelinating glial cell development.…”

Section: Supplemental and Source Data Formentioning

confidence: 99%

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Cd59 and inflammation orchestrate Schwann cell development

Wiltbank

Steisnon

Criswell

et al. 2022

Preprint

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Efficient neurotransmission is essential for organism survival and is enhanced by myelination. However, the genes that regulate myelin and myelinating glial cell development have not been fully characterized. Data from our lab and others demonstrates that cd59, which encodes for a small GPI-anchored glycoprotein, is highly expressed in developing zebrafish, rodent, and human oligodendrocytes (OLs) and Schwann cells (SCs), and that patients with CD59 dysfunction develop neurological dysfunction during early childhood. Yet, the function of CD59 in the developing nervous system is currently undefined. In this study, we demonstrate that cd59 is expressed in a subset of developing SCs. Using cd59 mutant zebrafish, we show that developing SCs proliferate excessively, which leads to reduced myelin volume, altered myelin ultrastructure, and perturbed node of Ranvier assembly. Finally, we demonstrate that complement activity is elevated in cd59 mutants and that inhibiting inflammation restores SC proliferation, myelin volume, and nodes of Ranvier to wildtype levels. Together, this work identifies Cd59 and developmental inflammation as key players in myelinating glial cell development, highlighting the collaboration between glia and the innate immune system to ensure normal neural development.

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Section: Discussionmentioning

confidence: 99%

Section: Supplemental and Source Data Formentioning

confidence: 99%

Cd59 and inflammation orchestrate Schwann cell development

Wiltbank

Steisnon

Criswell

et al. 2022

Preprint

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“…Myelin breakdown products must be degraded around the myelin sheath, astrocytes and microglia (Wang et al, 2020) or, more likely, transported back to the oligodendrocyte cell body for degradation by established organelles such as lysosomes and proteasomes. The literature is rife with reports of axon glial interactions but scant about molecules involved in myelin-axon communication (Nave and Trapp, 2008;Reiter and Bongarzone, 2020;Wang et al, 2020). Particularly important to this field may be findings related to lysosomal brain disorders (Fraldi et al, 2016;Kett and Dauer, 2016;Kao et al, 2017;Yellajoshyula et al, 2017) as CORVET/HOPS proteins track to lysosomes in the endolysosomal system.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes

et al. 2021

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A founder mutation in human VPS11 ( Vacuolar Protein Sorting 11) was recently linked to a genetic leukoencephalopathy in Ashkenazi Jews that presents with the classical features of white matter disorders of the central nervous system (CNS). The neurological deficits include hypomyelination, hypotonia, gradual loss of vision, and seizures. However, the cells expressing the mutation were not identified. Here we describe, using immunocytochemistry, the strong expression of Vps11 in mouse oligodendrocytes and, specifically, its localization with Myelin Associated Glycoprotein (MAG) in the inner tongue of myelin. In longitudinal sections of myelin, it forms a bead-like structure, alternating with Myelin Basic Protein (MBP). Immunofluorescent staining with Vps11 and neurofilament proteins indicates the absence of Vps11 in axons in vivo. Finally, changes in Vps11 expression are associated with altered proteolipid protein (PLP) levels based upon mice with duplications or deletions of the Plp1 gene. To determine potential functional contributions of Vps11, we combined Vps11 with Platelet Derived Growth Factor Receptor-α (PDGFRα) in vitro and in vivo: in both conditions, co-localization of the two proteins was frequently found in round vesicles of OPCs/oligodendrocytes, suggesting retrograde transport for degradation by the endolysosomal system. Neuron-to-glial communication has been invoked to explain degenerative changes in myelin followed by degenerative changes in axons, and vice versa; but to our knowledge, no specific proteins in retrograde transport from the myelin inner tongue to oligodendrocyte perikarya have been identified. The identification of mutations in VPS11 and its localization at the axon-myelin interface should open new avenues of research.

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“…There are many studies on the physiological, pathological, diagnostic, and therapeutic aspects of exosomes in axonal regeneration after nerve injury [ 144 ]. Exosomes in the nerve system are secreted by neurons, neural crest cells, and other supporting cells, such as astrocytes, oligodendrocytes, microglia, SCs (Schwann cells), and endothelial cells [ 145 , 146 ]. In CNS, exosomes have shown a promising lead for diagnosis of disease progression, treatment, and drug delivery in neurodegenerative diseases [ 147 , 148 ].…”

Section: Exosomes In Peripheral Nerve Repair and Regenerationmentioning

confidence: 99%

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Wan

Hussain

Behfar

et al. 2022

IJMS

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Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.

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The Role of Vesicle Trafficking and Release in Oligodendrocyte Biology

Cited by 15 publications

References 99 publications

Cd59 and inflammation orchestrate Schwann cell development

Cd59 and inflammation orchestrate Schwann cell development

Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

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