Myosin II is a negative regulator of oligodendrocyte morphological differentiation

Wang, Haibo; Rusielewicz, Tomasz; Tewari, Ambika; Leitman, Ellen M.; Einheber, Steven; Melendez‐Vasquez, Carmen V.

doi:10.1002/jnr.23036

Cited by 43 publications

(72 citation statements)

References 53 publications

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“…Although the conclusions of these studies implicate modulation of both the inflammatory response and blood–brain barrier permeability as the main cause underlying these beneficial effects, it is not implausible that enhanced differentiation (Kippert et al, 2007; Wang et al, 2012) and OL-mediated remyelination (this work) could also account for improved clinical recovery.…”

Section: Discussionmentioning

confidence: 83%

Accelerated repair of demyelinated CNS lesions in the absence of non‐muscle myosin IIB

Rusielewicz

Nam

Damanakis

et al. 2014

Glia

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The oligodendrocyte (OL), the myelinating cell of the central nervous system, undergoes dramatic changes in the organization of its cytoskeleton as it differentiates from a precursor (OPC) to a myelin-forming cell. These changes include an increase in its branching cell processes, a phenomenon necessary for OL to myelinate multiple axon segments. We have previously shown that levels and activity of non-muscle myosin II (NMII), a regulator of cytoskeletal contractility, decrease as a function of differentiation and that inhibition of NMII increases branching and myelination of OL in coculture with neurons. We have also found that mixed glial cell cultures derived from NMIIB knockout mice display an increase in mature myelin basic protein-expressing OL compared to wild type cultures. We have now extended our studies to investigate the role of NMIIB ablation on myelin repair following focal demyelination by lysolecithin. To this end, we generated an oligodendrocyte-specific inducible knockout model using a Plp-driven promoter in combination with a temporally activated CRE-ER fusion protein. Our data indicate that conditional ablation of NMII in adult mouse brain, expedites lesion resolution and remyelination by Plp+ oligodendrocyte-lineage cells when compared to that observed in control brains. Taken together, these data validate the function of NMII as that of a negative regulator of OL myelination in vivo and provide a novel target for promoting myelin repair in conditions such as multiple sclerosis.

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Section: Discussionmentioning

confidence: 83%

Accelerated repair of demyelinated CNS lesions in the absence of non‐muscle myosin IIB

Rusielewicz

Nam

Damanakis

et al. 2014

Glia

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“…55,56) Myosin II is a hexameric complex composed of 2 myosin heavy chains, 2 MLCs, and 2 essential light chains. 57) Levels of non-muscle myosin II decrease as a function of oligodendrocyte differentiation and inhibition of myosin activity increases branching and myelination, 58,59) although their expression levels correlate negatively with myelination. 59,60) The demyelination observed in neuropathic pain due to nerve lysophosphatidic acid-induced injury occurs on Schwann cells.…”

Section: Discussionmentioning

confidence: 99%

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

Harada

Matsuura

Takano

et al. 2016

Biological & Pharmaceutical Bulletin

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Central post-stroke pain (CPSP) is one of the complications of cerebral ischemia and neuropathic pain syndrome. At present, there are few studies of pain in regions such as the spinal cord or sciatic nerve in cerebral ischemic animal models. To identify proteomic changes in the spinal cord and sciatic nerve in global cerebral ischemic model mice, in the present study we performed an investigation using proteomic methods. In a comparison between the intensity of protein spots obtained from a sham and that from a bilateral carotid artery occulusion (BCAO) in spinal cord and sciatic nerve, the levels of 10 (spinal cord) and 7 (sciatic nerve) protein spots were altered. The protein levels in the spinal cord were significantly increased in N G ,N Gdimethylarginine dimethylaminohydrolase 1 (DDAH1), 6-phosphogluconolactonase isoform 1, and precursor apoprotein A-I and decreased in dihydropyrimidinase-related protein 2 (CRMP-2), enolase 1B, rab guanosine 5′-diphosphate (GDP) dissociation inhibitor beta, septin-2 isoform a, isocitrate dehydrogenase subunit alpha, cytosolic malate dehydrogenase, and adenosine triphosphate synthase. The protein levels in the sciatic nerve were significantly increased in a mimecan precursor, myosin light chain 1/3, and myosin regulatory light chain 2 (MLC2), and decreased in dihydropyrimidinase-related protein 3 (CRMP-4), protein disulfideisomerase A3, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, and B-type creatine kinase. In addition, CRMP-2 and CRMP-4 protein levels were decreased, and DDAH1 and MLC2 protein levels were increased on day 1 after BCAO using Western blotting. These results suggested that changes in these proteins may be involved in the regulation of CPSP.Key words global ischemia; pain; spinal cord; sciatic nerve; proteome Cerebral stroke remains one of the leading causes of death and disability worldwide.1) Recent insights into the basic mechanism involved in ischemic stroke indicate that endothelial dysfunctions along with oxidative stress and neuroinflammation are key elements in the occurrence and development of ischemic brain damage that results in cell damage and death.2,3) Many clinical symptoms can manifest after strokes, including motor deficits, cognitive dysfunction, language problems, emotional disturbances, social maladjustment, somatosensory dysfunction, and central pain. 4,5) Cerebral stroke occasionally induces central post-stroke pain (CPSP) that manifests as burning pain, throbbing pain, aching pain, slashing pain, allodynia, and hyperalgesia, either continuously or intermittently on the affected side.6,7) CPSP is known to be one of the neuropathic pain.8) Neuropathic pain is defined as "pain initiated or caused by a primary lesion or dysfunction of the nervous system." It can be a debilitating and difficult condition to treat and is often resistant to simple analgesics, requiring additional analgesic treatment. 9)Some hypotheses of the pathophysiological mechanisms of somatosensory dysfunction have been proposed to explain CPSP symptoms, such as the ...

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“…The identification of regulators of actin polymerization suggests a direct effect of Wnt signaling on SC process extension and lamellipodia formation. In particular, Fyn kinase has been shown to control cytoskeletal modifications and lamellae extension in oligodendrocytes (44,45). The identified transcription factors could also directly affect SC differentiation: Jun is a known negative regulator of SC differentiation and myelination (2,46).…”

Section: Mechanisms Of Axonal Sorting Deficits In β-Catenin Mutant Scmentioning

confidence: 99%

Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development

Grigoryan¹,

Stein²,

Qi³

et al. 2013

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

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Myosin II is a negative regulator of oligodendrocyte morphological differentiation

Cited by 43 publications

References 53 publications

Accelerated repair of demyelinated CNS lesions in the absence of non‐muscle myosin IIB

Accelerated repair of demyelinated CNS lesions in the absence of non‐muscle myosin IIB

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development

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