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Aggregation state determines the localization and function of M1- and M23-aquaporin-4 in astrocytes.

ABSTRACT: The astrocyte water channel aquaporin-4 (AQP4) is expressed as heterotetramers of M1 and M23 isoforms in which the presence of M23-AQP4 promotes formation of large macromolecular aggregates termed orthogonal arrays. Here, we demonstrate that the AQP4 aggregation state determines its subcellular localization and cellular functions. Individually expressed M1-AQP4 was freely mobile in the plasma membrane and could diffuse into rapidly extending lamellipodial regions to support cell migration. In contrast, M23-AQP4 formed large arrays that did not diffuse rapidly enough to enter lamellipodia and instead stably bound adhesion complexes and polarized to astrocyte end-feet in vivo. Co-expressed M1- and M23-AQP4 formed aggregates of variable size that segregated due to diffusional sieving of small, mobile M1-AQP4-enriched arrays into lamellipodia and preferential interaction of large, M23-AQP4-enriched arrays with the extracellular matrix. Our results therefore demonstrate an aggregation state-dependent mechanism for segregation of plasma membrane protein complexes that confers specific functional roles to M1- and M23-AQP4.

SUBMITTER: Smith AJ

PROVIDER: S-EPMC3926963 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Aggregation state determines the localization and function of M1- and M23-aquaporin-4 in astrocytes.

Smith Alex J AJ Jin Byung-Ju BJ Ratelade Julien J Verkman Alan S AS

The Journal of cell biology 20140210 4

The astrocyte water channel aquaporin-4 (AQP4) is expressed as heterotetramers of M1 and M23 isoforms in which the presence of M23-AQP4 promotes formation of large macromolecular aggregates termed orthogonal arrays. Here, we demonstrate that the AQP4 aggregation state determines its subcellular localization and cellular functions. Individually expressed M1-AQP4 was freely mobile in the plasma membrane and could diffuse into rapidly extending lamellipodial regions to support cell migration. In co ...[more]

PMID: 24515349

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Dataset Information

Aggregation state determines the localization and function of M1- and M23-aquaporin-4 in astrocytes.

Publications

Aggregation state determines the localization and function of M1- and M23-aquaporin-4 in astrocytes.

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