A novel RING-H2 motif protein downregulated by axotomy: Its characteristic localization at the postsynaptic density of axosomatic synapse

Abstract

Axonal injury and its repair are common and basic neuropathological processes in the CNS, and are composed of a complex of events in a molecular term. In order to get a comprehensive understanding of these processes, we isolated several known and unknown genes which were upor downregulated in the facial nucleus after transection of the facial nerve by a subtractive/differential screening. Among them, we focus on one downregulated gene, named Neurodap 1, because this gene encodes a novel protein carrying the RING-H2 sequence motif categorized in the zinc finger family, lmmunoelectron microscopic analysis revealed that the protein encoded by Neurodap1, Neurodap1, was distributed mainly on the cytoplasmic side of the membranes constituting endoplasmic reticulum and Golgi apparatus, supporting the notion of a previously postulated function of RING-H2 motif proteins, that is, involvement in the protein sorting machinery. More interestingly, Neurodap1 was also bound to the postsynaptic density (PSD) region of axosomatic synapses. This fact suggests that Neurodapl is associated with a specific system sorting proteins to PSD. Therefore, Neurodap1, a newly identified protein as an axotomy-suppressed gene product, might play a significant role in synaptic communication and plasticity through the control of the formation of PSD for maintaining vital functions of nerve cells.