Aquaporin-4 is absent at the sarcolemma and at perivascular astrocyte endfeet in alpha 1-syntrophin knockout mice

alpha 1-Syntrophin, a member of dystrophin-associated proteins, is expresse d at the sar colemma and at perivascular astrocytes, and participates in pr otein-protein interactions through its PDZ domain. Aquaporin-4 (AQP4) is th e predominant water channel protein in the brain, and also expressed at the sarcolemma of fast-twitch muscle fibers. AQP4 is concentrated in orthogona l array particles (OAPs), and its expression has been reported to be decrea sed at the sarcolemma of dystrophin-deficient mdx mice. We examined whether alpha 1-syntrophin targets AQP4 at the sarcolemma. Immunohistochemistry sh owed that AQP4 is absent at the sarcolemma in alpha 1-syntrophin knockout m ice and that its expression is also lost from the perivascular astrocyte en dfeet. On the other hand, expression of AQP4 is not decreased at the sarcol emma of the knockout mice in the neonatal stage. Moreover, AQP4 is expresse d in lung, stomach, and kidney of wild-type and alpha 1-syntrophin null mic e. Our results show that alpha 1-syntrophin is a key molecule to localize A QP4 to the sarcolemma of mature fast myofibers and astrocyte endfeet, but A QP4 is targeted to the plasma membrane by different molecules in lung, stom ach, and kidney.