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Integrin signaling in oligodendrocytes and its importance in CNS myelination.

O'Meara RW, Michalski JP, Kothary R - J Signal Transduct (2010)

Bottom Line: To tailor novel therapeutics to halt or reverse disease process, we require a better understanding of oligodendrocyte biology and of the molecular mechanisms that initiate myelination.Integrin-mediated signaling is crucial to the proliferation, survival, and maturation of oligodendrocytes through the activation of downstream signaling pathways involved in cytoskeletal remodeling.Here, we review the current understanding of this important signaling axis and its role in oligodendrocyte biology and ultimately in the myelination of axons within the CNS.

View Article: PubMed Central - PubMed

Affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.

ABSTRACT
Multiple sclerosis is characterized by repeated demyelinating attacks of the central nervous system (CNS) white matter tracts. To tailor novel therapeutics to halt or reverse disease process, we require a better understanding of oligodendrocyte biology and of the molecular mechanisms that initiate myelination. Cell extrinsic mechanisms regulate CNS myelination through the interaction of extracellular matrix proteins and their transmembrane receptors. The engagement of one such receptor family, the integrins, initiates intracellular signaling cascades that lead to changes in cell phenotype. Oligodendrocytes express a diverse array of integrins, and the expression of these receptors is developmentally regulated. Integrin-mediated signaling is crucial to the proliferation, survival, and maturation of oligodendrocytes through the activation of downstream signaling pathways involved in cytoskeletal remodeling. Here, we review the current understanding of this important signaling axis and its role in oligodendrocyte biology and ultimately in the myelination of axons within the CNS.

No MeSH data available.


Related in: MedlinePlus

Representation of integrin receptor expression over the course of oligodendrocyte development. Oligodendrocytes originate as precursor cells with simple morphology and subsequently differentiate into pro-oligodendrocytes, characterized by extension of intricate process meshworks. The final stages of maturation involve wrapping of axons in multiple layers of myelin membrane. Integrin receptors are differentially expressed during oligodendrocyte maturation. αvβ1-integrin and α6β1-integrin are strongly expressed in the oligodendrocyte precursor phase, whereas αvβ5-integrin is strongly expressed in late stages of development. αvβ8 is principally expressed in early and late stages of oligodendrocyte maturation, while αvβ3-integrin is expressed strongly in intermediate stages.
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fig1: Representation of integrin receptor expression over the course of oligodendrocyte development. Oligodendrocytes originate as precursor cells with simple morphology and subsequently differentiate into pro-oligodendrocytes, characterized by extension of intricate process meshworks. The final stages of maturation involve wrapping of axons in multiple layers of myelin membrane. Integrin receptors are differentially expressed during oligodendrocyte maturation. αvβ1-integrin and α6β1-integrin are strongly expressed in the oligodendrocyte precursor phase, whereas αvβ5-integrin is strongly expressed in late stages of development. αvβ8 is principally expressed in early and late stages of oligodendrocyte maturation, while αvβ3-integrin is expressed strongly in intermediate stages.

Mentions: Expression of integrins is developmentally regulated, and different cell types express diverse arrays of integrins depending on their stage of differentiation. Oligodendrocytes are no exception, variably expressing α and β subunits based on developmental stage (Figure 1). For example, αvβ8-integrin is expressed strongly by precursor and mature oligodendrocytes, whereas αvβ3-integrin is expressed predominantly during intermediate maturity stages [21]. Newly formed oligodendrocytes strongly express α6β1-integrin, whereas αvβ5 expression increases as oligodendrocytes mature [20, 22, 23].


Integrin signaling in oligodendrocytes and its importance in CNS myelination.

O'Meara RW, Michalski JP, Kothary R - J Signal Transduct (2010)

Representation of integrin receptor expression over the course of oligodendrocyte development. Oligodendrocytes originate as precursor cells with simple morphology and subsequently differentiate into pro-oligodendrocytes, characterized by extension of intricate process meshworks. The final stages of maturation involve wrapping of axons in multiple layers of myelin membrane. Integrin receptors are differentially expressed during oligodendrocyte maturation. αvβ1-integrin and α6β1-integrin are strongly expressed in the oligodendrocyte precursor phase, whereas αvβ5-integrin is strongly expressed in late stages of development. αvβ8 is principally expressed in early and late stages of oligodendrocyte maturation, while αvβ3-integrin is expressed strongly in intermediate stages.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101883&req=5

fig1: Representation of integrin receptor expression over the course of oligodendrocyte development. Oligodendrocytes originate as precursor cells with simple morphology and subsequently differentiate into pro-oligodendrocytes, characterized by extension of intricate process meshworks. The final stages of maturation involve wrapping of axons in multiple layers of myelin membrane. Integrin receptors are differentially expressed during oligodendrocyte maturation. αvβ1-integrin and α6β1-integrin are strongly expressed in the oligodendrocyte precursor phase, whereas αvβ5-integrin is strongly expressed in late stages of development. αvβ8 is principally expressed in early and late stages of oligodendrocyte maturation, while αvβ3-integrin is expressed strongly in intermediate stages.
Mentions: Expression of integrins is developmentally regulated, and different cell types express diverse arrays of integrins depending on their stage of differentiation. Oligodendrocytes are no exception, variably expressing α and β subunits based on developmental stage (Figure 1). For example, αvβ8-integrin is expressed strongly by precursor and mature oligodendrocytes, whereas αvβ3-integrin is expressed predominantly during intermediate maturity stages [21]. Newly formed oligodendrocytes strongly express α6β1-integrin, whereas αvβ5 expression increases as oligodendrocytes mature [20, 22, 23].

Bottom Line: To tailor novel therapeutics to halt or reverse disease process, we require a better understanding of oligodendrocyte biology and of the molecular mechanisms that initiate myelination.Integrin-mediated signaling is crucial to the proliferation, survival, and maturation of oligodendrocytes through the activation of downstream signaling pathways involved in cytoskeletal remodeling.Here, we review the current understanding of this important signaling axis and its role in oligodendrocyte biology and ultimately in the myelination of axons within the CNS.

View Article: PubMed Central - PubMed

Affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.

ABSTRACT
Multiple sclerosis is characterized by repeated demyelinating attacks of the central nervous system (CNS) white matter tracts. To tailor novel therapeutics to halt or reverse disease process, we require a better understanding of oligodendrocyte biology and of the molecular mechanisms that initiate myelination. Cell extrinsic mechanisms regulate CNS myelination through the interaction of extracellular matrix proteins and their transmembrane receptors. The engagement of one such receptor family, the integrins, initiates intracellular signaling cascades that lead to changes in cell phenotype. Oligodendrocytes express a diverse array of integrins, and the expression of these receptors is developmentally regulated. Integrin-mediated signaling is crucial to the proliferation, survival, and maturation of oligodendrocytes through the activation of downstream signaling pathways involved in cytoskeletal remodeling. Here, we review the current understanding of this important signaling axis and its role in oligodendrocyte biology and ultimately in the myelination of axons within the CNS.

No MeSH data available.


Related in: MedlinePlus