Aim: 

Aquaporin-4 (AQP4) is expressed by the astrocytes of the brain cortex and spinal cord and arranged in the plasma membrane in a well organized structure called orthogonal arrays of particles (OAPs). AQP4 and its organization in OAPs are altered in Duchenne Muscular Dystrophy. In this study, to gain insight into the mechanisms linking AQP4 and the dystrophin complex, we analyzed their organization in the plasma membrane during the differentiation of a progenitor cell into a mature astrocyte.

Methods: 

This study was performed using primary astrocyte cultures and neural stem cells (NSCs) isolated from embryonic brain. Immunofluorescence experiments were analyzed by confocal microscopy and the plasma membrane oganization of AQP4 and the Dystrophin Associated Proteins (DAPs) by BN/SDS-PAGE. TIRF microscopy was used for water transport measurements.

Results: 

NSCs expressed significant levels of functional AQP4 water channel together with dystrophin, beta-distroglycan and alfa-syntrophin, indicating a possible role for these proteins during stem cell development. Interestingly, by BN/SDS-PAGE we found that AQP4, dystrophin (Dp71), a-syntrophin and ß-dystroglycan colocalize in the same multiproteic complex (MPCs) only in mature astrocytes and not in NSCs.

Conclusion: 

This is the first study showing the expression of AQP4 together with dystrophin and the DAPs at the level of NSCs and that NCSs differentiation in astrocytes represent an ideal model to study the molecular basis of the interaction between AQP4 and DAPs. Further studies will be focused to investigate the role of this interaction during stem cell development and in mature astrocytes.