The activity of proteins that control Ca in cells is regulated by the Ca-signal itself, and are called autoregulatory. The autoregulatory nature of the NaAF signal in Ca-homeostasis was revealed earlier by its ability to control its own intracellular level by gene-expression (Ray TK, 2013, doi: 10.12688/f1000research.2-165.v2 and 10.12688/f1000research.2-241.v1). However, based on similar literature evidences the NaAF-autoregulation can also occur both at the transcriptional and posttranscriptional levels (see below): The universal Na-pump regulator, NaAF thus, can be generalized as an autoregulatory Ca-Sensor.
The importance of Na-pump is undeniable in processing the area-specific thought signals (electromagnetic) in brain, like the ability of brain for ‘Global Positioning’ in everyday tasks . Numerous area-specific αβ isoforms of the Na-pump in brain are driven by the universal NaAF to generate the voltage signal (EMF) across the cell plasma membranes for whole-cell signaling purposes.
The NaAF self-regulates itself for upholding an appropriate intracellular concentration via gene-expression by histone phosphorylation (see above Ray 2013) possibly aided by Ca, since it is long known that Ca regulates the transcription of a number of genes (Santella L, Carafoli E.FASEB J 11: 1091–1109, 1997). In addition, emerging evidences do indicate that the microRNAs expression might participate in the regulation of NaAF level.
In cardiovascular diseases the proteins involved in Ca-handling are regulated by the microRNAs. There are characteristic changes in the expression of a group of specific microRNAs accompanying cardiac hypertrophy and heart failure ((Rooiz et al PNAS 105, 13027–13032, 2008)). Thus, considering the NaAF as an autoregulatory Ca-sensor for Na-pump-regulation, the microRNAs may also be involved in regulating the NaAF-dependent Na-pump (Na, K-ATPase) function in heart as well as in brain. In brain, the microRNAs seem to regulate the NaAF level by interfering with its translation from the mRNA.
Thus, the universal Na-pump regulator, NaAF, is expected to self-regulate its intracellular level via gene-expression (mentioned earlier), as well as using microRNA to regulate its mRNA-translation in various brain areas. Hence, for furthering the knowledge and understanding in many of our health problems, detailed studies on the mechanisms of NaAF regulation of the vital Na-pump will be essential.
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