Laminin‐1 increases motility, path‐searching, and process dynamism of rat and mouse Muller glial cells in vitro: Implication of relationship between cell behavior and formation of retinal morphology

Méhes, Előd; Czirók, András; Hegedűs, Balázs; Vicsek, Tamás; Jancsik, Veronika

doi:10.1002/cm.10062

Cited by 17 publications

(20 citation statements)

References 17 publications

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“…Although laminin‐1 is not produced by Müller cells as demonstrated by our study and that of Méhes et al . (2002), laminin‐1 originating from other cells has been described as a major constituent of the ECM separating the ILM, where Müller cell endfeet are concentrated, from the vitreous body (Méhes et al . 2002).…”

Section: Resultssupporting

confidence: 82%

Dystroglycan and Kir4.1 coclustering in retinal Müller glia is regulated by laminin‐1 and requires the PDZ‐ligand domain of Kir4.1

Noël

Belda

Guadagno

et al. 2005

Journal of Neurochemistry

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Inwardly rectifying potassium (Kir) channels in Mü ller glia play a critical role in the spatial buffering of potassium ions that accumulate during retinal activity. To this end, Kir channels show a polarized subcellular distribution with the predominant channel subunit in Mü ller glia, Kir4.1, clustered in the endfeet of these cells at the inner limiting membrane. However, the molecular mechanisms underlying their distribution have yet to be identified. Here, we show that laminin, agrin and a-dystroglycan (DG) codistribute with Kir4.1 at the inner limiting membrane in the retina and that laminin-1 induces the clustering of a-DG, syntrophin and Kir4.1 in Mü ller cell cultures. In addition, we found that a-DG clusters were enriched for agrin and sought to investigate the role of agrin in their formation using recombinant C-agrins. Both C-agrin 4,8 and C-agrin 0,0 failed to induce a-DG clustering and neither of them potentiated the a-DG clustering induced by laminin-1. Finally, our data reveal that deletion of the PDZ-ligand domain of Kir4.1 prevents their laminin-induced clustering. These findings indicate that both laminin-1 and a-DG are involved in the distribution of Kir4.1 to specific Mü ller cell membrane domains and that this process occurs via a PDZ-domain-mediated interaction. Thus, in the basal lamina laminin is an essential regulator involved in clearing excess potassium released during neuronal activity, thereby contributing to the maintenance of normal synaptic transmission in the retina.

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Section: Resultssupporting

confidence: 82%

Dystroglycan and Kir4.1 coclustering in retinal Müller glia is regulated by laminin‐1 and requires the PDZ‐ligand domain of Kir4.1

Noël

Belda

Guadagno

et al. 2005

Journal of Neurochemistry

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“…However, in the Lama1 ⌬ homozygous retina, many Müller cell processes were truncated and lacked end-feet. These abnormalities suggest that laminin ␣1 is important in path searching of Müller glial cells in vivo as has already been demonstrated for laminin-111 in vitro (38). The differences observed between these mouse models in regard to retinal Müller cells and ganglion cells are likely to reflect allelic differences and their effects on laminin ␣1 protein structure and function as well as subsequent protein interactions.…”

Section: Discussionmentioning

confidence: 63%

“…We hypothesize that the nmf223 mutation in Lama1, Y265C, could lead to an abnormal mesh formation in the basement membrane by decreasing the number of ␣1 LN binding partners in vivo, despite the presence of interactions between ␤1 LN and ␥1 LN. In addition, the ability of laminin 111 to act as a chemoattractant for Müller cells (38) may be hindered by the Y265C mutation.…”

Section: Discussionmentioning

confidence: 99%

Mutations in Lama1 Disrupt Retinal Vascular Development and Inner Limiting Membrane Formation

Edwards

Mammadova‐Bach

Alpy

et al. 2010

Journal of Biological Chemistry

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The Neuromutagenesis Facility at the Jackson Laboratory generated a mouse model of retinal vasculopathy, nmf223, which is characterized clinically by vitreal fibroplasia and vessel tortuosity. nmf223 homozygotes also have reduced electroretinogram responses, which are coupled histologically with a thinning of the inner nuclear layer. The nmf223 locus was mapped to chromosome 17, and a missense mutation was identified in Lama1 that leads to the substitution of cysteine for a tyrosine at amino acid 265 of laminin ␣1, a basement membrane protein.Despite normal localization of laminin ␣1 and other components of the inner limiting membrane, a reduced integrity of this structure was suggested by ectopic cells and blood vessels within the vitreous. Immunohistochemical characterization of nmf223 homozygous retinas demonstrated the abnormal migration of retinal astrocytes into the vitreous along with the persistence of hyaloid vasculature. The Y265C mutation significantly reduced laminin N-terminal domain (LN) interactions in a bacterial twohybrid system. Therefore, this mutation could affect interactions between laminin ␣1 and other laminin chains. To expand upon these findings, a Lama1 null mutant, Lama1 tm1.1Olf , was generated that exhibits a similar but more severe retinal phenotype than that seen in nmf223 homozygotes. The increased severity of the Lama1 null mutant phenotype is probably due to the complete loss of the inner limiting membrane in these mice. This first report of viable Lama1 mouse mutants emphasizes the importance of this gene in retinal development. The data presented herein suggest that hypomorphic mutations in human LAMA1 could lead to retinal disease.

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“…To study the mechanisms of microglia recruitment to sites of infection, we first established co-cultures of neurons and GFP-positive microglia from Cx3Cr1 +/GFP mice and per- of microglia with more advanced statistical approaches [24,43,44], which required co-cultures of microglia with very sparsely distributed cells. Since this was not feasible with neuronal cultures, we took advantage that astrocytes are also infected with PRV under in vitro conditions [24].…”

Section: Virus-infected Cells Are Recognised and Engulfed By Microglimentioning

confidence: 99%

Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms

et al. 2018

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Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain’s immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1885-0) contains supplementary material, which is available to authorized users.

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Laminin‐1 increases motility, path‐searching, and process dynamism of rat and mouse Muller glial cells in vitro: Implication of relationship between cell behavior and formation of retinal morphology

Cited by 17 publications

References 17 publications

Dystroglycan and Kir4.1 coclustering in retinal Müller glia is regulated by laminin‐1 and requires the PDZ‐ligand domain of Kir4.1

Dystroglycan and Kir4.1 coclustering in retinal Müller glia is regulated by laminin‐1 and requires the PDZ‐ligand domain of Kir4.1

Mutations in Lama1 Disrupt Retinal Vascular Development and Inner Limiting Membrane Formation

Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms

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