Delprat Benjamin, Bibert Stéphanie, Geering Käthi
Département de Pharmacologie et Toxicologie, Université de Lausanne, rue du Bugnon 27, 1005 Lausanne, Suisse.
Med Sci (Paris). 2006 Jun-Jul;22(6-7):633-8. doi: 10.1051/medsci/20062267633.
Members of the FXYD protein family are small membrane proteins which are characterized by an FXYD motif, two conserved glycines and a serine residue. FXYD proteins show a tissue-specific distribution. Recent evidence suggests that 6 out of 7 FXYD proteins, FXYD1 (phospholemman), FXYD2 (gamma subunit of Na,K-ATPase), FXYD3 (Mat-8), FXYD4 (CHIF), FXYD5 (Ric) and FXYD7 associate with Na,K-ATPase and modulate its transport properties e.g. its Na+ and/or its K+ affinity in a distinct way. These results highlight the complex regulation of Na+ and K+ transport which is necessary to ensure proper tissue functions such as renal Na+-reabsorption, muscle contractility and neuronal excitability. Moreover, mutation of a conserved glycine residue into an arginine residue in FXYD2 has been linked to cases of human hypomagnesemia indicating that dysregulation of Na,K-ATPase by FXYD proteins may be implicated in pathophysiological states. A better characterization of this novel regulatory mechanism of Na,K-ATPase may help to better understand its role in physiological and pathophysiological conditions.
FXYD蛋白家族成员是一类小的膜蛋白，其特征在于具有一个FXYD基序、两个保守的甘氨酸和一个丝氨酸残基。FXYD蛋白呈现出组织特异性分布。最近的证据表明，7种FXYD蛋白中的6种，即FXYD1（磷膜蛋白）、FXYD2（钠钾ATP酶的γ亚基）、FXYD3（Mat-8）、FXYD4（CHIF）、FXYD5（Ric）和FXYD7与钠钾ATP酶相关联，并以独特的方式调节其转运特性，例如其对Na⁺和/或K⁺的亲和力。这些结果突出了Na⁺和K⁺转运的复杂调节，这对于确保诸如肾脏Na⁺重吸收、肌肉收缩性和神经元兴奋性等正常组织功能是必要的。此外，FXYD2中一个保守的甘氨酸残基突变为精氨酸残基与人类低镁血症病例有关，这表明FXYD蛋白对钠钾ATP酶的调节异常可能与病理生理状态有关。对钠钾ATP酶这种新型调节机制的更好表征可能有助于更好地理解其在生理和病理生理条件下的作用。
