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Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membrane.
Glia. 2008 Apr 15; 56(6):597-610.GLIA

Abstract

The dystrophin-associated proteins (DAPs) complex consisting of dystroglycan, syntrophin, dystrobrevin, and sarcoglycans in muscle cells is associated either with dystrophin or its homolog utrophin. In rat retina, a similar complex was found associated with dystrophin-Dp71 that serves as an anchor for the inwardly rectifying potassium channel Kir4.1 and the aqueous pore, aquaporin-4 (AQP4). Here, using immunofluorescence imaging of isolated retinal Müller glial cells and co-immunoprecipitation experiments performed on an enriched Müller glial cells end-feet fraction, we investigated the effect of Dp71 deletion on the composition, anchoring, and membrane localization of the DAPs-Kir4.1 and/or -AQP4 complex. Two distinct complexes were identified in the end-feet fraction associated either with Dp71 or with utrophin. Upon Dp71 deletion, the corresponding DAPs complex was disrupted and a compensating utrophin upregulation was observed, accompanied by diffuse overall staining of Kir4.1 along the Müller glial cells and redistribution of the K(+) conductance. Dp71 deficiency was also associated with a marked reduction of AQP4 and beta-dystroglycan expression. Furthermore, it was observed that the Dp71-DAPs dependent complex could be, at least partially, associated with a specific membrane fraction. These results demonstrate that Dp71 has a central role in the molecular scaffold responsible for anchoring AQP4 and Kir4.1 in Müller cell end-feet membranes. They also show that despite its close relationship to the dystrophin proteins and its correlated upregulation, utrophin is only partially compensating for the absence of Dp71 in Müller glial cells.

Authors+Show Affiliations

Université Pierre et Marie Curie-Paris6, UMR-S 592, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18286645

Citation

Fort, Patrice E., et al. "Kir4.1 and AQP4 Associate With Dp71- and utrophin-DAPs Complexes in Specific and Defined Microdomains of Müller Retinal Glial Cell Membrane." Glia, vol. 56, no. 6, 2008, pp. 597-610.
Fort PE, Sene A, Pannicke T, et al. Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membrane. Glia. 2008;56(6):597-610.
Fort, P. E., Sene, A., Pannicke, T., Roux, M. J., Forster, V., Mornet, D., Nudel, U., Yaffe, D., Reichenbach, A., Sahel, J. A., & Rendon, A. (2008). Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membrane. Glia, 56(6), 597-610. https://doi.org/10.1002/glia.20633
Fort PE, et al. Kir4.1 and AQP4 Associate With Dp71- and utrophin-DAPs Complexes in Specific and Defined Microdomains of Müller Retinal Glial Cell Membrane. Glia. 2008 Apr 15;56(6):597-610. PubMed PMID: 18286645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membrane. AU - Fort,Patrice E, AU - Sene,Abdoulaye, AU - Pannicke,Thomas, AU - Roux,Michel J, AU - Forster,Valerie, AU - Mornet,Dominique, AU - Nudel,Uri, AU - Yaffe,David, AU - Reichenbach,Andreas, AU - Sahel,Jose A, AU - Rendon,Alvaro, PY - 2008/2/21/pubmed PY - 2008/6/21/medline PY - 2008/2/21/entrez SP - 597 EP - 610 JF - Glia JO - Glia VL - 56 IS - 6 N2 - The dystrophin-associated proteins (DAPs) complex consisting of dystroglycan, syntrophin, dystrobrevin, and sarcoglycans in muscle cells is associated either with dystrophin or its homolog utrophin. In rat retina, a similar complex was found associated with dystrophin-Dp71 that serves as an anchor for the inwardly rectifying potassium channel Kir4.1 and the aqueous pore, aquaporin-4 (AQP4). Here, using immunofluorescence imaging of isolated retinal Müller glial cells and co-immunoprecipitation experiments performed on an enriched Müller glial cells end-feet fraction, we investigated the effect of Dp71 deletion on the composition, anchoring, and membrane localization of the DAPs-Kir4.1 and/or -AQP4 complex. Two distinct complexes were identified in the end-feet fraction associated either with Dp71 or with utrophin. Upon Dp71 deletion, the corresponding DAPs complex was disrupted and a compensating utrophin upregulation was observed, accompanied by diffuse overall staining of Kir4.1 along the Müller glial cells and redistribution of the K(+) conductance. Dp71 deficiency was also associated with a marked reduction of AQP4 and beta-dystroglycan expression. Furthermore, it was observed that the Dp71-DAPs dependent complex could be, at least partially, associated with a specific membrane fraction. These results demonstrate that Dp71 has a central role in the molecular scaffold responsible for anchoring AQP4 and Kir4.1 in Müller cell end-feet membranes. They also show that despite its close relationship to the dystrophin proteins and its correlated upregulation, utrophin is only partially compensating for the absence of Dp71 in Müller glial cells. SN - 0894-1491 UR - https://www.unboundmedicine.com/medline/citation/18286645/Kir4_1_and_AQP4_associate_with_Dp71__and_utrophin_DAPs_complexes_in_specific_and_defined_microdomains_of_Müller_retinal_glial_cell_membrane_ L2 - https://doi.org/10.1002/glia.20633 DB - PRIME DP - Unbound Medicine ER -