Induction of oligodendrocyte differentiation by activators of adenylate cyclase

Raible, David W.; McMorris, F. Arthur

doi:10.1002/jnr.490270107

Cited by 76 publications

(58 citation statements)

References 7 publications

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“…Separate experiments next investigated the functional consequences of signaling through the TPR nuclear pathway. In this connection, cAMP has been reported to influence OLG development (38,40), in part through activation of the transcription factor CREB (43). Consistent with this notion, our results demonstrated that stimulation of OLG nuclei with the TPR agonist U46619 (5 M) did indeed lead to activation of CREB, as indicated by an increase in phospho-CREB over basal levels (Fig.…”

Section: Fig 1 Expression and Distribution Of G Proteins In Opcs Andsupporting

confidence: 79%

“…OLGs mature, TPR coupling with G q would lead to activation of the calcium-dependent signaling pathways involved in the modulation of different kinases (mitogen-activated protein kinase/extracellular signal-regulated kinase) affecting OLG differentiation (36). Finally, as nuclear TPR-G s complexes are formed, TPR stimulation would lead to cAMP-mediated activation of CREB, which is involved in MBP expression and OLG survival (38,40). While the results described above provide evidence that TPR activation can modulate nuclear signaling events, they do not establish the source of TXA 2 in this cellular compartment.…”

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confidence: 99%

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A Novel Nuclear Signaling Pathway for Thromboxane A₂ Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

Mir

Breton

2008

Molecular and Cellular Biology

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The present study investigated G protein expression, localization, and functional coupling to thromboxane A2 receptors (TPRs) during oligodendrocyte (OLG) development. It was found that as OLGs mature, the expression levels of Gq increase while those of G13 decrease. In contrast, the expression levels of Gs, Go, and Gi do not change significantly. Localization studies revealed that Gq, G13, and Gi are present only in the extranuclear compartment, whereas Gs and Go are found in both the extranuclear and the nuclear compartments. Purification of TPR-G protein complexes demonstrated that TPRs couple to both Gq and G13 in the extranuclear compartment but only to Gs in the nuclear compartment. Furthermore, functional analysis revealed that stimulation of nuclear TPR in OLGs stimulates CREB phosphorylation and myelin basic protein transcription and increases survival. Collectively, these results demonstrate that (i) OLGs selectively modulate the expression of certain G proteins during development, (ii) G proteins are differentially localized in OLGs leading to subcellular compartmentalization, (iii) TPRs couple to Gq and G13 in the extranuclear compartment and to Gs only in the nucleus, (iv) mature OLGs have a functional nuclear TPR-Gs signaling pathway, and (v) nuclear TPR signaling can stimulate CREB phosphorylation and myelin gene transcription and increase cell survival. These findings represent a novel paradigm for selective modulation of G protein-coupled receptor-G protein signaling during cell development.

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Section: Fig 1 Expression and Distribution Of G Proteins In Opcs Andsupporting

confidence: 79%

mentioning

confidence: 99%

A Novel Nuclear Signaling Pathway for Thromboxane A₂ Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

Mir

Breton

2008

Molecular and Cellular Biology

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“…Although the in vivo endogenous binding partner(s) for Gpr17 in oligodendrocyte development are not known, this GPCR can bind uracil nucleotides, cysteinyl leukotrienes, and oxysterols [59,60], and work in vitro with small molecule agonists suggests that Gpr17 can signal through Gα i/o , G s , and G q proteins [61,62]. In vitro, Gα i/o protein signaling inhibits adenylyl cyclase signaling and subsequent OPC differentiation [62], consistent with previous reports implicating cAMP in the promotion of oligodendrocyte development [63]. In the future, it will be interesting to determine if Gpr17 function in vivo is dependent on Cxcl12 as a ligand, either directly or via Gpr17/Cxcr4 heterodimers [56].…”

Section: Gpr17 and Gpr37 In Oligodendrocyte Differentiationsupporting

confidence: 85%

G Protein-Coupled Receptors in Myelinating Glia

Mogha¹,

D’Rozario²,

Monk

2017

Trends in Pharmacological Sciences

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The G protein-coupled receptor (GPCR) super-family represents the largest class of functionally selective drug targets for disease modulation and therapy. GPCRs have been studied in great detail in central nervous system (CNS) neurons, yet these important molecules have been relatively understudied in glia. In recent years, however, exciting new roles for GPCRs in glial cell biology have emerged. Here, we focus on key roles for GPCRs in a specialized subset of glia, myelinating glia. We highlight recent work firmly establishing GPCRs as regulators of myelinating glial cell development and myelin repair. These advancements expand our understanding of myelinating glial cell biology and underscore the utility of targeting GPCRs to promote myelin repair in human disease. KeywordsG protein-coupled receptor (GPCR); myelination; Schwann cell; oligodendrocyte; remyelination An overview of G protein-coupled receptors in the nervous systemThe G protein-coupled receptor (GPCR) super-family of seven transmembrane (7TM) receptors comprises the largest class of cell membrane receptors [1]. GPCRs are activated by myriad stimuli including peptides, hormones, light, proteolytic processing of their Ntermini, small molecules, and more traditional protein ligands [2,3]. GPCRs have emerged as major pharmacological drug targets due to their key roles in a variety of physiological functions in disease and health, and GPCR modulators represent at least one-third of all clinically marketed drugs [4]. GPCRs can be classified into five families using the phylogenetically based GRAFS system: glutamate, rhodopsin, adhesion, frizzled, and secretin [5]. Glutamate is a major excitatory neurotransmitter in the nervous system, and * Correspondence: monkk@wustl.edu (K.R. Monk). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of interest statementThe authors declare no competing conflicts. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript accordingly, glutamate receptors have been studied in great detail with regard to their key roles in synaptic transmission, synapse formation, axon guidance, and development of neuronal circuits [6,7]. The rhodopsin family has by far the greatest number of GPCRs, and members are involved in photoreception and neurotransmission [5]. Frizzled GPCRs are activated by wingless/int (Wnt) proteins and control numerous cellular processes including neural crest development, patterning and adult neurogenesis [8]. Secretin receptors are classic hormone receptors, some of which have neuroprotective functions in the central nervou...

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“…29 Briefly, CNS from newborn mice were stripped of meninges, mechanically dissociated, seeded into T-75 flasks, and maintained in OM5 media with 10% FBS. After 2 to 4 weeks, cultures were trypsinized and incubated in RPMI (10% FBS, without phenol red) in suspension for 60 minutes at 37°C to allow for the re-expression of trypsinized surface markers.…”

Section: Microglia Isolation From Mixed Glial Culturesmentioning

confidence: 99%

Disproportionate Recruitment of CD8+ T Cells into the Central Nervous System by Professional Antigen-Presenting Cells

Carson

Reilly

Sutcliffe

et al. 1999

The American Journal of Pathology

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Inappropriate immune responses , thought to exacerbate or even to initiate several types of central nervous system (CNS) neuropathology , could arise from failures by either the CNS or the immune system. The extent that the inappropriate appearance of antigenpresenting cell (APC) function contributes to CNS inflammation and pathology is still under debate. Therefore , we characterized the response initiated when professional APCs (dendritic cells) presenting non-CNS antigens were injected into the CNS. These dendritic cells expressed numerous T-cell chemokines , but only in the presence of antigen did leukocytes accumulate in the ventricles , meninges, subarachnoid spaces, and injection site. Within the CNS parenchyma , the injected dendritic cells migrated preferentially into the white matter tracts , yet only a small percentage of the recruited leukocytes entered the CNS parenchyma , and then only in the white matter tracts. Although T-cell recruitment was antigen specific and thus mediated by CD4 ؉ T cells in the models used here , CD8 ؉ T cells accumulated in numbers equal to or greater than that of CD4 ؉ T cells. Few of the recruited T cells expressed activation markers (CD25 and VLA-4) , and those that did were primarily in the meninges , injection site , ventricles , and perivascular spaces but not in the parenchyma. These results indicate that 1) the CNS modulates the cellular composition and activation states of responding T-cell populations and that 2) myelin-restricted inflammation need not be initiated by a myelin-specific antigen. (Am J Pathol 1999, 154:481-494)

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Induction of oligodendrocyte differentiation by activators of adenylate cyclase

Cited by 76 publications

References 7 publications

A Novel Nuclear Signaling Pathway for Thromboxane A₂ Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

A Novel Nuclear Signaling Pathway for Thromboxane A₂ Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

G Protein-Coupled Receptors in Myelinating Glia

Disproportionate Recruitment of CD8+ T Cells into the Central Nervous System by Professional Antigen-Presenting Cells

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Induction of oligodendrocyte differentiation by activators of adenylate cyclase

Cited by 76 publications

References 7 publications

A Novel Nuclear Signaling Pathway for Thromboxane A2 Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

A Novel Nuclear Signaling Pathway for Thromboxane A2 Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

G Protein-Coupled Receptors in Myelinating Glia

Disproportionate Recruitment of CD8+ T Cells into the Central Nervous System by Professional Antigen-Presenting Cells

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A Novel Nuclear Signaling Pathway for Thromboxane A₂ Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

A Novel Nuclear Signaling Pathway for Thromboxane A₂ Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation