SDF-1α and LPA modulate microglia potassium channels through rho gtpases to regulate cell morphology.

Abstract:

:Microglia are the resident immune cells of the brain, which are important therapeutic targets for regulating the inflammatory responses particularly neurodegeneration in the aging human brain. The activation, chemotaxis and migration of microglia are regulated through G-protein coupled receptors by chemokines such as stromal cell-derived factor (SDF)-1α and bioactive lysophospholipids such as lysophosphatidic acid (LPA). Potassium channels play important roles in microglial function and cell fate decisions; however, the regulation of microglial potassium channels has not been fully elucidated. Here we show reciprocal action of SDF-1α and LPA, on potassium currents through Kir2.1 channels in primary murine microglia. The potassium channel modulation is mediated by the same small GTPases, Rac and Rho that regulate the actin cytoskeleton. SDF-1α rapidly increased the Kir2.1 current amplitude and cell spreading. These effects were mimicked by dialysing the cells with constitutively active Rac1 protein, and they were blocked by inhibiting the phosphatidylinositol 3-kinase (PI3K) with wortmannin. In contrast, LPA and constitutively active RhoA decreased the Kir2.1 currents and stimulated cell contraction. Thus, SDF-1α and LPA regulate both the actin cytoskeleton and the Kir2.1 potassium channels through the same Rho GTPase signaling pathways. The inhibition of Kir2.1 with chloroethylclonidine produced cell contraction independently of chemokine action. This suggests that potassium channels are essential for the morphological phenotype and functioning of microglia. In conclusion, the small GTPases, Rac and Rho, modulate Kir2.1 channels and block of Kir2.1 channels causes changes in microglia morphology.

journal_name

Glia

journal_title

Glia

authors

Muessel MJ,Harry GJ,Armstrong DL,Storey NM

doi

10.1002/glia.22543

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

1620-8

issue

10

eissn

0894-1491

issn

1098-1136

journal_volume

61

pub_type

杂志文章

相关文献

GLIA文献大全
  • Atrial natriuretic peptide-like (ANP-LIR) and ANP prohormone immunoreactive astrocytes and neurons of human cerebral cortex.

    abstract::Atrial natriuretic peptide (ANP) represents a family of related peptides originally isolated from cardiac atria that have potent natriuretic, diuretic, and vasorelaxant properties. ANP has previously been localized in neurons of the rat brain in regions subserving cardiovascular functions and fluid/electrolyte balance...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440120308

    authors: McKenzie JC,Berman NE,Thomas CR,Young JK,Compton LY,Cothran LN,Liu WL,Klein RM

    更新日期:1994-11-01 00:00:00

  • VEGF as a modulator of the innate immune response in glioblastoma.

    abstract::VEGF is an important factor in tumor vascularization and used as target for anti-angiogenic treatment strategies in glioma. In this study, we demonstrate for the first time that VEGF is a modulator of the innate immune response with suppressive effects on the immunologic and pro-angiogenic function of microglia/macrop...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23234

    authors: Turkowski K,Brandenburg S,Mueller A,Kremenetskaia I,Bungert AD,Blank A,Felsenstein M,Vajkoczy P

    更新日期:2018-01-01 00:00:00

  • Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality.

    abstract::CNS glia exhibit a variety of gap junctional interactions: between neighboring astrocytes, between neighboring oligodendrocytes, between astrocytes and oligodendrocytes, and as 'reflexive' structures between layers of myelin in oligodendrocytes. Together, these junctions are thought to form a network facilitating abso...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.21179

    authors: Magnotti LM,Goodenough DA,Paul DL

    更新日期:2011-07-01 00:00:00

  • The CpG island shore of the GLT-1 gene acts as a methylation-sensitive enhancer.

    abstract::Astrocytic lineage commitment and brain region-dependent specialization of glia are partly ascribed to epigenetic processes. Clearance of glutamate is an essential task, which astrocytes assume in a temporal-spatial fashion by distinct glutamate transporter expression. Glutamate transporter subtype 1 (GLT-1) is predom...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22353

    authors: Perisic T,Holsboer F,Rein T,Zschocke J

    更新日期:2012-09-01 00:00:00

  • Differential expression of protein tyrosine kinase genes during microglial activation.

    abstract::Protein tyrosine kinase (PTK) activity is abundant in microglia, but the PTKs that participate in their activation have not been identified. For these studies, we used three paradigms to characterize PTK expression during microglial activation: resting and activated microglia were bulk fractionated from the adult brai...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10101

    authors: Krady JK,Basu A,Levison SW,Milner RJ

    更新日期:2002-10-01 00:00:00

  • Prostaglandin E1, E2, and cholera toxin increase transcription of the brain creatine kinase gene in human U87 glioblastoma cells.

    abstract::The creatine kinase isoenzymes play an important role in maintaining ATP levels in some cell types during times of high energy demand. We have previously shown in primary cell cultures from rat brain that glial cells express much higher levels of brain creatine kinase (CKB) mRNA than neurons. In a separate earlier stu...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440150410

    authors: Kuzhikandathil EV,Molloy GR

    更新日期:1995-12-01 00:00:00

  • Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes.

    abstract::Recent studies have suggested that Nkx6.2/Gtx and Nkx2.2 homeodomain transcription factors are involved in the regulation of oligodendrocyte maturation and/or myelination which occur predominantly in postnatal stages. However, their cellular specificity in postnatal central nervous system has not been characterized an...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20937

    authors: Cai J,Zhu Q,Zheng K,Li H,Qi Y,Cao Q,Qiu M

    更新日期:2010-03-01 00:00:00

  • Focal adhesion kinase is required for endothelin-induced cell cycle progression of cultured astrocytes.

    abstract::When the brain is damaged, astrocytes often cause hyperplasia resulting in glial scar formation at the injured sites. Endothelins (ETs) have been shown to be involved in the pathophysiologic responses of astrocytes, including proliferation. In this study, we examined the mechanisms underlying the ET-induced astrocytic...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10240

    authors: Koyama Y,Yoshioka Y,Matsuda T,Baba A

    更新日期:2003-08-01 00:00:00

  • Reactive astrocytes in myelin-deficient rat optic nerve reveal an altered distribution of orthogonal arrays of particles (OAP).

    abstract::Reactive astrocytes are a common feature of various pathological conditions within the CNS. Morphological changes of reactive astrocytes include an altered nucleus-cytoplasm relationship, nuclear indentations, an increased amount of intermediate filaments, and an immunologically immature phenotype. Additionally, the n...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440050404

    authors: Rohlmann A,Gocht A,Wolburg H

    更新日期:1992-01-01 00:00:00

  • Fish optic nerve oligodendrocytes support axonal regeneration of fish and mammalian retinal ganglion cells.

    abstract::Segments from adult fish and rat retinae were explanted on myelin-marker expressing oligodendrocytes derived from the regenerating goldfish optic nerve. Fish axons grew in high density and even rat retinal axons regenerated to considerable length on the surface of the fish oligodendrocytes, suggesting that this type o...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440080102

    authors: Bastmeyer M,Bähr M,Stuermer CA

    更新日期:1993-05-01 00:00:00

  • Functional properties of retinal Müller cells following transplantation to the anterior eye chamber.

    abstract::Two types of glial cells occur in the retina, Müller cells and astrocytes. These cells share several structural features such as extending endfeet onto blood vessels of the retina. Retinal vessels express a tight blood-retinal barrier which is comparable to the blood-brain barrier (BBB) of the CNS. While astrocytes ha...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440070205

    authors: Small RK,Watkins BA,Munro PM,Liu D

    更新日期:1993-02-01 00:00:00

  • Remote astrocytic response as demonstrated by glial fibrillary acidic protein immunohistochemistry in the visual cortex of dorsal lateral geniculate nucleus lesioned rats.

    abstract::The reaction of astroglia was investigated after unilateral destruction of the dorsal lateral geniculate nucleus in the primary visual cortex of adult albino rats. The destruction of the dorsal lateral geniculate nucleus was performed by stereotaxic injections of ibotenic acid, and the location was verified in Nissl s...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440030410

    authors: Hajós F,Kálmán M,Zilles K,Schleicher A,Sótonyi P

    更新日期:1990-01-01 00:00:00

  • Novel microtubule-associated protein-2 isoform is expressed early in human oligodendrocyte maturation.

    abstract::We have identified a developmentally regulated, oligodendrocyte-specific protein, designated microtubule-associated protein-2 expressing exon 13 (MAP-2+13), in the human central nervous system (CNS). Monoclonal antibodies directed against MAP-2+13 labeled oligodendrocytes in the white matter of human fetal spinal cord...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Shafit-Zagardo B,Davies P,Rockwood J,Kress Y,Lee SC

    更新日期:2000-02-01 00:00:00

  • Transplanted glial restricted precursor cells improve neurobehavioral and neuropathological outcomes in a mouse model of neonatal white matter injury despite limited cell survival.

    abstract:OBJECTIVE:Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy and other neurocognitive deficits in prematurely-born children, and no restorative therapies exist. Our objective was to determine the fate and effect of glial restricted precursor cell (GRP) transplantation in an ischemic mouse model ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22764

    authors: Porambo M,Phillips AW,Marx J,Ternes K,Arauz E,Pletnikov M,Wilson MA,Rothstein JD,Johnston MV,Fatemi A

    更新日期:2015-03-01 00:00:00

  • Ultrastructural study of phagocytic activities of young astrocytes in injured neonatal rat brain following intracerebral injection of colloidal carbon.

    abstract::The cellular reaction to injury in the mature central nervous system (CNS) has been extensively studied in both man and animals, while a detailed study of the reaction of the immature CNS to injury is lacking in the literature. This study was undertaken to elucidate the response of young astrocytes following injection...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440010306

    authors: Al-Ali SY,Al-Zuhair AG,Dawod B

    更新日期:1988-01-01 00:00:00

  • DBcAMP effect on the expression of GFAP and of its encoding mRNA in astroglial primary cultures.

    abstract::Short term and chronic dBcAMP effects on the expression of glial fibrillary acidic protein (GFAP) in astroglial primary cultures are investigated. Short (48 h) and long (more than 7 days) treatments with the cAMP derivative induce both cell shape changes and an increase in GFAP immunolabelling. Such effects are only a...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440040310

    authors: Le Prince G,Fages C,Rolland B,Nunez J,Tardy M

    更新日期:1991-01-01 00:00:00

  • NMDA receptor couples Rac1-GEF Tiam1 to direct oligodendrocyte precursor cell migration.

    abstract::Oligodendrocyte precursor cells (OPCs) originate from restricted regions of the brain and migrate into the developing white matter, where they differentiate into oligodendrocytes and myelinate axons in the central nervous system (CNS). The molecular mechanisms that orchestrate these long distance trips of OPCs to popu...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22578

    authors: Xiao L,Hu C,Yang W,Guo D,Li C,Shen W,Liu X,Aijun H,Dan W,He C

    更新日期:2013-12-01 00:00:00

  • Neu differentiation factor regulates tau protein and mRNA in cultured neonatal oligodendrocytes.

    abstract::Axonal signals activate myelinogenesis via regulation of the extent to which oligodendrocyte (OLG) processes wrap around the axon. The cytoskeleton in OLG processes is actively involved in myelination and is a putative target for axonal regulation of myelination. The axon-associated neuregulins may regulate the cytosk...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.1079

    authors: LoPresti P,Muma NA,De Vries GH

    更新日期:2001-08-01 00:00:00

  • An update on human astrocytes and their role in development and disease.

    abstract::Human astrocytes provide trophic as well as structural support to the surrounding brain cells. Furthermore, they have been implicated in many physiological processes important for central nervous system function. Traditionally astrocytes have been considered to be a homogeneous class of cells, however, it has increasi...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23771

    authors: de Majo M,Koontz M,Rowitch D,Ullian EM

    更新日期:2020-04-01 00:00:00

  • Differential expression of neuropsin and protease M/neurosin in oligodendrocytes after injury to the spinal cord.

    abstract::Neuropsin and protease M/neurosin are serine proteases expressed by neurons and glial cells, and serve a variety of functions in the central nervous system (CNS). The current study demonstrates changes in the expression of these proteases following hemisection of the mouse spinal cord. Within unlesioned spinal cord, n...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20058

    authors: Terayama R,Bando Y,Takahashi T,Yoshida S

    更新日期:2004-11-01 00:00:00

  • Tissue remodeling in periplaque regions of multiple sclerosis spinal cord lesions.

    abstract::Our knowledge of multiple sclerosis (MS) neuropathology has benefited from a number of studies that provided an in-depth description of plaques and, more recently, diffuse alterations of the normal-appearing white or grey matter. However, there have been few studies focusing on the periplaque regions surrounding demye...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22705

    authors: Lieury A,Chanal M,Androdias G,Reynolds R,Cavagna S,Giraudon P,Confavreux C,Nataf S

    更新日期:2014-10-01 00:00:00

  • Cellular distribution of superoxide dismutases in the rat CNS.

    abstract::Superoxide dismutase (SOD) is considered to be a major factor in protection of nervous tissue against excitotoxic and ischemic/hypoxic lesion. Controversial reports about the localization of SOD after such an insult prompted us to re-investigate immunocytochemically the localization of the enzyme in the brain and spin...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(20000101)29:1<25::aid-glia

    authors: Lindenau J,Noack H,Possel H,Asayama K,Wolf G

    更新日期:2000-01-01 00:00:00

  • Repetitive injury and absence of monocytes promote astrocyte self-renewal and neurological recovery.

    abstract::Unlike microglia and NG2 glia, astrocytes are incapable of migrating to sites of injury in the posttraumatic cerebral cortex, instead relying on proliferation to replenish their numbers and distribution in the affected region. However, neither the spectrum of their proliferative repertoire nor their postinjury distrib...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23893

    authors: Lange Canhos L,Chen M,Falk S,Popper B,Straub T,Götz M,Sirko S

    更新日期:2021-01-01 00:00:00

  • Transcriptional control of myelination and remyelination.

    abstract::Myelination is an evolutionary recent differentiation program that has been independently acquired in vertebrates by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. Therefore, it is not surprising that regulating transcription factors differ substantially between both...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.23636

    authors: Sock E,Wegner M

    更新日期:2019-11-01 00:00:00

  • Trimethyltin-induced expression of GABA and vimentin immunoreactivities in astrocytes of the rat brain.

    abstract::Adult Sprague-Dawley rats were given a single dose of trimethyltin chloride (TMT). Three days following treatment, a neuronal alteration was observed in the CA3c pyramidal cell layer of hippocampus which was not accompanied by any apparent astrocyte reaction. At 1 as well as 2 weeks after treatment, a gliosis in hippo...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440110410

    authors: Andersson H,Luthman J,Olson L

    更新日期:1994-08-01 00:00:00

  • Neuroinflammation in Alzheimer's disease and prion disease.

    abstract::Alzheimer's disease (AD) and prion disease are characterized neuropathologically by extracellular deposits of Abeta and PrP amyloid fibrils, respectively. In both disorders, these cerebral amyloid deposits are co-localized with a broad variety of inflammation-related proteins (complement factors, acute-phase protein, ...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.10146

    authors: Eikelenboom P,Bate C,Van Gool WA,Hoozemans JJ,Rozemuller JM,Veerhuis R,Williams A

    更新日期:2002-11-01 00:00:00

  • Mice lacking NT-3, and its receptor TrkC, exhibit profound deficiencies in CNS glial cells.

    abstract::Neurotrophin-3 (NT-3) and its receptor TrkC are known to be important for neuronal survival. More recently, NT-3 has been implicated as playing a role in oligodendrocyte (OL) proliferation and survival in vitro. Examination of NT-3 and TrkC knockout mice revealed a reduction in NT-3-dependent neurons. To date, no stud...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Kahn MA,Kumar S,Liebl D,Chang R,Parada LF,De Vellis J

    更新日期:1999-04-01 00:00:00

  • Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis.

    abstract::The consequences of sublytic terminal complement complex (TCC) assembly on Schwann cell proliferation and apoptosis were examined by using purified complement proteins (C5*-9) or antibody-sensitized Schwann cells in the presence of a serum that was depleted of the seventh component of complement (C7dHS) and reconstitu...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(200004)30:2<187::aid-glia8

    authors: Dashiell SM,Rus H,Koski CL

    更新日期:2000-04-01 00:00:00

  • Cognitive deficits in mice lacking Nsun5, a cytosine-5 RNA methyltransferase, with impairment of oligodendrocyte precursor cells.

    abstract::Williams-Beuren syndrome (WBS) is a microdeletion disorder with cognitive phenotype. NSUN5 gene, which encodes a cytosine-5 RNA methyltransferase, is located in WBS deletion locus. To investigate the influence of NSUN5 deletion on cognitive behaviors, we produced single-gene Nsun5 knockout (Nsun5-KO) mice. Here, we re...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23565

    authors: Zhang T,Chen P,Li W,Sha S,Wang Y,Yuan Z,Shen B,Chen L

    更新日期:2019-04-01 00:00:00

  • Regulation of carbachol- and histamine-induced inositol phospholipid hydrolysis in a human oligodendroglioma.

    abstract::A stable cell line derived from a human oligodendroglioma (HOG) was used to study the regulation of muscarinic- and histamine receptor-mediated phosphoinositide hydrolysis. Both carbachol and histamine increased inositol monophosphate (InsP) accumulation in a dose- and time-dependent manner in the presence of lithium ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440050206

    authors: Post GR,Dawson G

    更新日期:1992-01-01 00:00:00