Department of Molecular Physiology and Neurobiology, University of Wrocław, Sienkiewicza 21, 50-335 Wrocław, Poland.
Cells. 2022 May 21;11(10):1710. doi: 10.3390/cells11101710.
Recently, we have shown that the physiological roles of a multifunctional protein fructose 1,6-bisphosphatase 2 (FBP2, also called muscle FBP) depend on the oligomeric state of the protein. Here, we present several lines of evidence that in HL-1 cardiomyocytes, a forced, chemically induced reduction in the FBP2 dimer-tetramer ratio that imitates AMP and NAD action and restricts FBP2-mitochondria interaction, results in an increase in Tau phosphorylation, augmentation of FBP2-Tau and FBP2-MAP1B interactions, disturbance of tubulin network, marked reduction in the speed of mitochondrial trafficking and increase in mitophagy. These results not only highlight the significance of oligomerization for the regulation of FBP2 physiological role in the cell, but they also demonstrate a novel, important cellular function of this multitasking protein-a function that might be crucial for processes that take place during physiological and pathological cardiac remodeling, and during the onset of diseases which are rooted in the destabilization of MT and/or mitochondrial network dynamics.
最近，我们已经证明了多功能蛋白果糖 1,6-二磷酸酶 2（FBP2，也称为肌型 FBP）的生理作用取决于其蛋白的寡聚状态。在这里，我们提供了几条证据表明，在 HL-1 心肌细胞中，一种强制的、化学诱导的降低 FBP2 二聚体-四聚体比例的方法可以模拟 AMP 和 NAD 的作用，并限制 FBP2 与线粒体的相互作用，从而导致 Tau 磷酸化增加，FBP2-Tau 和 FBP2-MAP1B 相互作用增强，微管网络紊乱，线粒体运输速度明显减慢，自噬增加。这些结果不仅强调了寡聚化对于调节 FBP2 在细胞中生理作用的重要性，而且还证明了这种多功能蛋白的一个新的重要细胞功能——这种功能可能对于发生在生理和病理性心脏重构过程中以及起源于 MT 和/或线粒体网络动力学不稳定的疾病的发生过程中至关重要。
