Béguin Pascal, Crambert Gilles, Monnet-Tschudi Florianne, Uldry Marc, Horisberger Jean-Daniel, Garty Haim, Geering Käthi
Institute of Pharmacology and Toxicology, University of Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
EMBO J. 2002 Jul 1;21(13):3264-73. doi: 10.1093/emboj/cdf330.
Recently, corticosteroid hormone-induced factor (CHIF) and the gamma-subunit, two members of the FXYD family of small proteins, have been identified as regulators of renal Na,K-ATPase. In this study, we have investigated the tissue distribution and the structural and functional properties of FXYD7, another family member which has not yet been characterized. Expressed exclusively in the brain, FXYD7 is a type I membrane protein bearing N-terminal, post-translationally added modifications on threonine residues, most probably O-glycosylations that are important for protein stabilization. Expressed in Xenopus oocytes, FXYD7 can interact with Na,K-ATPase alpha 1-beta 1, alpha 2-beta 1 and alpha 3-beta 1 but not with alpha-beta 2 isozymes, whereas, in brain, it is only associated with alpha 1-beta isozymes. FXYD7 decreases the apparent K(+) affinity of alpha 1-beta 1 and alpha 2-beta 1, but not of alpha 3-beta1 isozymes. These data suggest that FXYD7 is a novel, tissue- and isoform-specific Na,K-ATPase regulator which could play an important role in neuronal excitability.
最近，皮质类固醇激素诱导因子（CHIF）和γ亚基这两个FXYD小蛋白家族成员已被确定为肾钠钾ATP酶的调节因子。在本研究中，我们研究了FXYD7（另一个尚未被表征的家族成员）的组织分布及其结构和功能特性。FXYD7仅在大脑中表达，是一种I型膜蛋白，其N端苏氨酸残基有翻译后添加的修饰，很可能是对蛋白质稳定很重要的O-糖基化修饰。在非洲爪蟾卵母细胞中表达时，FXYD7可与钠钾ATP酶α1-β1、α2-β1和α3-β1相互作用，但不与α-β2同工酶相互作用，而在大脑中，它仅与α1-β同工酶相关。FXYD7降低了α1-β1和α2-β1的表观K(+)亲和力，但不影响α3-β1同工酶的表观K(+)亲和力。这些数据表明，FXYD7是一种新型的、组织和同工型特异性的钠钾ATP酶调节因子，可能在神经元兴奋性中起重要作用。
