Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly...

CASK interacting nucleosome assembly protein (CINAP) modulates gene expression and its abundance in cultured neurons is regulated by synaptic activity. To further study the function of CINAP in vivo, we examined the temporal and spatial expression profiles of CINAP. CINAP was widely expressed in different regions of adult mouse brain, including the cerebral cortex, hippocampus, striatum, hypothalamus, cerebellum, and two adult brain regions known to generate progenitor neurons. During early development, CINAP was also expressed in regions where neuronal progenitor cells were actively dividing, the ventricular and subventricular zones, suggesting that in addition to regulating gene expression in mature neurons, CINAP may also play a role in dividing cells. Since the hypothalamus responds to several physiological responses, we examined whether CINAP protein levels in the paraventricular nucleus (PVN) of the hypothalamus are regulated by changes in osmolality achieved through oral administration of hypertonic saline. Compared with control mice, mice treated with hypertonic saline expressed higher CINAP protein levels in the PVN, supporting a role of CINAP in neural response in vivo. Using confocal microscopic analysis, a significant amount of CINAP was found in the cytoplasm of neurons. Biochemical fractionation further confirmed that CINAP was associated with synapses, suggesting a translocation of CINAP protein from synapse to the nucleus. Consistent with this speculation, nuclear CINAP levels in the PVN were higher in hypertonic saline-treated mice than those who drank water. CINAP may be regulated through changes in protein stability and nuclear translocation in neurons.