Astrocytic and neuronal localization of the scaffold protein Na+/H+ exchanger regulatory factor 2 (NHERF-2) in mouse brain.

The Na+/H+ exchanger regulatory factor 2 (NHERF-2) is a scaffold protein that regulates cellular signaling by forming protein complexes. Several proteins known to interact with NHERF-2 are abundantly expressed in the central nervous system, but little is known about NHERF-2 localization in the brain. By using immunohistochemistry combined with light and electron microscopy, we found that many populations of astrocytes, as well as some populations of neurons, were immunopositive for NHERF-2 throughout the mouse brain. Quantitative analysis of the subcellular distribution of NHERF-2 immunostaining in four brain structures, cerebral cortex, hippocampus, striatum, and cerebellar cortex, showed that NHERF-2 was expressed mainly in astrocytic processes but was also sometimes observed in both pre- and postsynaptic neuronal elements. NHERF-2 immunostaining was associated mainly with the plasma membrane of neurons and astrocytes. However, NHERF-2 immunoreactivity was also observed in association with synaptic vesicles in putative glutamatergic axon terminals. The subcellular localization of NHERF-2 in brain is consistent with a role for NHERF-2 in forming complexes between cell surface and cytosolic proteins, and the preferential expression of NHERF-2 in astrocytes suggests that this scaffold protein may play an important role in astrocytic physiology.