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

• DOI: 10.1083/jcb.201308118
• Publication Date: 2014-02-11T04:39:46Z
• Authors: Alex J. Smith; Byung-Ju Jin; Julien Ratelade; Alan S. Verkman
• Keywords: Aquaporin 4; Lamellipodium; Pseudopodia

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