Involvement of aquaporin‐4 in laminin‐enhanced process formation of mouse astrocytes in 2D culture: Roles of dystroglycan and α‐syntrophin in aquaporin‐4 expression

Sato, Junya; Horibe, Sayo; Kawauchi, Shoji; Sasaki, Naoto; Hirata, Ken‐ichi; Rikitake, Yoshiyuki

doi:10.1111/jnc.14548

Cited by 26 publications

(37 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, AQP4 is retained in perivascular astrocyte membranes through anchoring via α-Syn to the DAP complex, which in turn is held in place through a dystroglycan bridge linked to laminin in the perivascular basal lamina (Neely et al 2001). Evidence has accrued to suggest that laminin and agrin are instructive in the sense that they initiate the build-up of the specific molecular assemblies in perivascular endfeet (Fallier-Becker et al 2011;Lunde et al 2015;Noell et al 2007Noell et al , 2009Noell et al , 2012Sato et al 2018;Tham et al 2016;Warth et al 2004;Wolburg et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain

et al. 2020

View full text Add to dashboard Cite

Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This complex includes α-syntrophin (α-Syn), which is believed to anchor aquaporin-4 (AQP4) to astrocytic endfoot membrane domains. We have previously shown that the size of the perivascular AQP4 pool differs considerably between brain regions in an α-Syn-dependent manner. Also, both AQP4 and α-Syn occur at higher densities in endfoot membrane domains facing pericytes than in endfoot membrane domains facing endothelial cells. The heterogeneous distribution of AQP4 at the regional and capillary level has been attributed to a direct interaction between AQP4 and α-Syn. This would be challenged (1) if the microdistributions of laminin and agrin fail to align with those of DAP and AQP4 and (2) if targeted deletion of α-Syn leads to a loss of laminin and/or agrin. Here, we provide the first detailed and quantitative analysis of laminin and agrin in brain basal laminae of mice. We show that the microdistributions of these molecules vary in a fashion that is well aligned with the previously reported microdistribution of AQP4. We also demonstrate that the expression patterns of laminin and agrin are insensitive to targeted deletion of α-Syn, suggesting that α-Syn deletion affects AQP4 directly and not indirectly via laminin or agrin. These data fill remaining voids in the current model of how key molecules are assembled and tethered at the gliovascular interface.

show abstract

Section: Discussionmentioning

confidence: 99%

Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain

et al. 2020

View full text Add to dashboard Cite

show abstract

“…12,13 The dystrophin-glycoprotein complex proteins, which are comprised of DG, dystrophin, Dp71, α-dystrobrevin, and α-syntrophin, provide a link between laminin and the cytoskeleton and are critical for the localization of AQP4. 32 Moreover, the levels of Dp71, α-DG, β-DG, and Agrin are the physiological markers of normal cells. In the present study, overexpression miR-320a and knockdown AQP4 significantly decreased the expressions of AQP4, α-syntrophin, β1-syntrophin, and Agrin, while markedly promoted the expressions of β-DG, α-DG, laminin, and Dp71.…”

Section: Discussionmentioning

confidence: 99%

microRNA‐320a prevent Müller cells from hypoxia injury by targeting aquaporin‐4

Chen

Yang

et al. 2020

J of Cellular Biochemistry

View full text Add to dashboard Cite

Müller cells are closely related to diabetic retinopathy (DR). Aquaporin-4 (AQP4) can effectively promote the diffusion of water across cellular membranes. However, the dynamic balance of water plays key role in many diseases, such as cerebral edema. Meanwhile, the unusual expression and distribution of AQP4 in the retina are the significant causes of ocular hypertension and reperfusion injury. To explore the functional significance between microRNA-320a (miR-320a) and AQP4 in pathological hypoxiainduced DR related retinal edema, we hypothesized that miR-320a regulates AQP4 expression and internalization to relieve the edema of Müller cells under the pathological retinal hypoxia stress by targeting AQP4, thereby attenuate the damage of Müller cells. Results demonstrated that miR-320a mimics inhibited the expressions of AQP4 in Müller cells. Furthermore, overexpression miR-320a protected Müller cells by suppressing superoxide anion. In addition, overexpression miR-320a markedly attenuated hypoxia-induced injury, significantly increased the cell viability, and promoted the internalization of AQP4. Furthermore, miR-320a can also regulate the stable anchoring of AQP4 on the cell membrane. Our study indicated that miR-320a may be a potential modulator which can mediate AQP4 expression and attenuate the hypoxia damage of Müller cells. In conclusion, miR-320a may be a potential target for DR therapy by targeting AQP4.

show abstract

“…These process-bearing astrocytes enabled us to investigate the mechanism of process formation and branching of astrocytes. For example, using these astrocytes, we found a key role for the interaction between laminin and DG in process formation and branching [16]. In the present study, we used these astrocytes to develop a novel in vitro co-culture model by which we can assess contact formation between astrocytes and blood vessels.…”

Section: Introductionmentioning

confidence: 98%

A novel in vitro co-culture model to examine contact formation between astrocytic processes and cerebral vessels

Kawauchi

Horibe

Sasaki

et al. 2019

Experimental Cell Research

Self Cite

View full text Add to dashboard Cite

Here, we developed a novel in vitro co-culture model, in which process-bearing astrocytes and isolated cerebral microvessels from mice were co-cultured. Astrocytes formed contacts with microvessels from both adult and neonatal mice. However, concentrated localization of the immunofluorescence signal for aquaporin-4 (AQP4) at contact sites between perivascular endfoot processes and blood vessels was only detected with neonatal mouse microvessels. Contact between astrocytic processes and microvessels was retained, whereas concentrated localization of AQP4 signal at contact sites was lost, by knockdown of dystroglycan or -syntrophin, reflecting polarized localization of AQP4 at perivascular regions in the brain. Further, using our in vitro co-culture model, we found that astrocytes predominantly extend processes to pericytes located at the abluminal surface of microvessels, providing additional evidence that this model is representative of the in vivo situation. Altogether, we have developed a novel in vitro co-culture model that can reproduce aspects of the in vivo situation and is useful for assessing contact formation between astrocytes and blood vessels. Highlights  A novel in vitro model was constructed by co-culturing process-bearing astrocytes and isolated cerebral microvessels from neonatal mice.  The polarized localization of AQP4 was detected at contact sites between astrocyte processes and microvessels.  The polarized localization of AQP4 at contact sites was disturbed by knockdown of -syntrophin or dystroglycan.  Astrocytes predominantly extended their processes to pericytes located at the abluminal surface of microvessels.

show abstract

Involvement of aquaporin‐4 in laminin‐enhanced process formation of mouse astrocytes in 2D culture: Roles of dystroglycan and α‐syntrophin in aquaporin‐4 expression

Cited by 26 publications

References 61 publications

Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain

Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain

microRNA‐320a prevent Müller cells from hypoxia injury by targeting aquaporin‐4

A novel in vitro co-culture model to examine contact formation between astrocytic processes and cerebral vessels

Contact Info

Product

Resources

About