Evolvability of the actin cytoskeleton in oligodendrocytes during central nervous system development and aging

Seixas, Ana I.; Azevedo, Maria M.; Faria, Joana Paes de; Fernandes, Diogo Castro; Pinto, Inês Mendes; Relvas, João B.

doi:10.1007/s00018-018-2915-8

Cited by 25 publications

(19 citation statements)

References 96 publications

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“…Likewise, OLG/OPC growth cones and their actin cytoskeletal dynamics are thought to play a key role in guiding the morphological changes associated with each of the stages of the OLG lineage. This idea is consistent with the critical functions ascribed to the actin cytoskeleton in controlling overall OLG morphology (Brown & Macklin, ; Domingues et al, ; Seixas et al, ). Notably, actin cytoskeletal mechanisms do not function in isolation and there is often crosstalk between actin‐ and microtubule‐based cytoskeletal activities.…”

Section: Introductionsupporting

confidence: 87%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and premyelinating OLGs, and during the process of active myelin wrapping, the forward movement of the leading edge of the myelin sheath's inner tongue along the axon.Almost all of these motile behaviors are driven by actin cytoskeletal dynamics initiated within a lamellipodial structure that is located at the tip of cellular OLG/OPC processes and is structurally as well as functionally similar to the neuronal growth cone. Accordingly, coordinated stoichiometries of actin filament (F-actin) assembly and disassembly at these OLG/OPC growth cones have been implicated in directing process outgrowth and guidance, and the initiation of myelination. Nonetheless, the functional importance of the OLG/OPC growth cone still remains to be fully understood, and, as a unique aspect of actin cytoskeletal dynamics, F-actin depolymerization and disassembly start to predominate at the transition from myelination initiation to myelin wrapping. This review provides an overview of the current knowledge about OLG/OPC growth cones, and it proposes a model in which actin cytoskeletal dynamics in OLG/OPC growth cones are a main driver for morphological transformations and motile behaviors. Remarkably, these activities, at least at the later stages of OLG maturation, may be regulated independently from the transcriptional gene expression changes typically associated with CNS myelination. K E Y W O R D Sactin cytoskeleton, growth cone, migration, myelination, oligodendrocyte

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Section: Introductionsupporting

confidence: 87%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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“…Myelin is a specialized membrane produced by oligodendrocytes and Schwann cells that spiral around axons, thereby enabling fast conduction of action potentials, and providing axonal support (Nave and Werner, 2014;Cohen et al, 2020). During myelination in the CNS, oligodendrocytes undergo extensive morphological changes (Bauer et al, 2009;Seixas et al, 2019;Brown and Macklin, 2020), beginning with the formation of exploratory processes that either make stable axonal contact or retract (Czopka et al, 2013;Almeida and Lyons, 2014). This initial contact is then followed by membrane ensheathment and wrapping, longitudinal extension of the forming myelin unit, and compaction of the myelin membrane layers (Osso and Chan, 2017;Stadelmann et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

N-Wasp Regulates Oligodendrocyte Myelination

et al. 2020

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Oligodendrocyte myelination depends on actin cytoskeleton rearrangement. Neural Wiskott-Aldrich syndrome protein (N-Wasp) is an actin nucleation factor that promotes polymerization of branched actin filaments. N-Wasp activity is essential for myelin membrane wrapping by Schwann cells, but its role in oligodendrocytes and CNS myelination remains unknown.Here we report that oligodendrocytes-specific deletion of N-Wasp in mice of both sexes resulted in hypomyelination (i.e., reduced number of myelinated axons and thinner myelin profiles), as well as substantial focal hypermyelination reflected by the formation of remarkably long myelin outfolds. These myelin outfolds surrounded unmyelinated axons, neuronal cell bodies, and other myelin profiles. The latter configuration resulted in pseudo-multimyelin profiles that were often associated with axonal detachment and degeneration throughout the CNS, including in the optic nerve, corpus callosum, and the spinal cord. Furthermore, developmental analysis revealed that myelin abnormalities were already observed during the onset of myelination, suggesting that they are formed by aberrant and misguided elongation of the oligodendrocyte inner lip membrane. Our results demonstrate that N-Wasp is required for the formation of normal myelin in the CNS. They also reveal that N-Wasp plays a distinct role in oligodendrocytes compared with Schwann cells, highlighting a difference in the regulation of actin dynamics during CNS and PNS myelination.

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“…The transporters ABCB6, ABCB7, ABCB8 and ABCB10 which belong to the half transporter B subfamily (ABCB group) are localized to the mitochondria 4 . ABCB6 is reported to localize in the plasma membrane, red blood cell membrane, melanosomes, mitochondria, and endolysosomes 5–10 . Mitochondrial ABC transporters along with mitoferrin (iron importer) and frataxin (storage/iron sensing regulator) control iron uptake and utilization in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Chronic Pressure Overload Results in Deficiency of Mitochondrial Membrane Transporter ABCB7 Which Contributes to Iron Overload, Mitochondrial Dysfunction, Metabolic Shift and Worsens Cardiac Function

Kumar

Sanawar

et al. 2019

Sci Rep

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We examined the hitherto unexplored role of mitochondrial transporters and iron metabolism in advancing metabolic and mitochondrial dysfunction in the heart during long term pressure overload. We also investigated the link between mitochondrial dysfunction and fluctuation in mitochondrial transporters associated with pressure overload cardiac hypertrophy. Left ventricular hypertrophy (LVH) was induced in 3-month-old male Wistar rats by constriction of the aorta using titanium clips. After sacrifice at the end of 6 and 15 months after constriction, tissues from the left ventricle (LV) from all animals were collected for histology, biochemical studies, proteomic and metabolic profiling, and gene and protein expression studies. LV tissues from rats with LVH had a significant decrease in the expression of ABCB7 and mitochondrial oxidative phosphorylation (mt-OXPHOS) enzymes, an increased level of lipid metabolites, decrease in the level of intermediate metabolites of pentose phosphate pathway and elevated levels of cytoplasmic and mitochondrial iron, reactive oxygen species (ROS) and autophagy-related proteins. Knockdown of ABCB7 in H9C2 cells and stimulation with angiotensin II resulted in increased ROS levels, ferritin, and transferrin receptor expression and iron overload in both mitochondria and cytoplasm. A decrease in mRNA and protein levels of mt-OXPHOS specific enzymes, mt-dynamics and autophagy clearance and activation of IGF-1 signaling were also seen in these cells. ABCB7 overexpression rescued all these changes. ABCB7 was found to interact with mitochondrial complexes IV and V. We conclude that in chronic pressure overload, ABCB7 deficiency results in iron overload and mitochondrial dysfunction, contributing to heart failure.

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Evolvability of the actin cytoskeleton in oligodendrocytes during central nervous system development and aging

Cited by 25 publications

References 96 publications

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

N-Wasp Regulates Oligodendrocyte Myelination

Chronic Pressure Overload Results in Deficiency of Mitochondrial Membrane Transporter ABCB7 Which Contributes to Iron Overload, Mitochondrial Dysfunction, Metabolic Shift and Worsens Cardiac Function

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