Although the function of the UBL domain of Tmub1/HOPS remains to be revealed in future Ginsenoside-F4 studies, it is interesting to speculate that the UBL domain can act as “pseudo” ubiquitin, which blocks ubiquitin function, similar to the dominant negative form of ubiquitin. It was indicated that a large portion of Tmub1/HOPS exists at recycling endosomes rather than at early endosomes. Internalized AMPARs for recycling enter to early endosomes and sorted to recycling endosomes for returning to the plasma membrane. NEEP21 interacts with the complex of GluR2 and GRIP at early endosomes and sorts the complex to the recycling pathway. The recycling of GluR2-containing AMPARs appears to be carried out by the association with endosomal proteins and peripheral factors throughout the pathway. Tmub1/ HOPS may act for the returning of GluR2-containing AMPARs to the plasma membrane, at recycling endosomes. Further, as the Orbifloxacin fluorescent intensity of intracellular GluR2 was not significantly changed, the spatiotemporal information of AMPARs after the stimulation is suggested to be consistent with previous reports. Tmub1/HOPS only affected the GluR2 subunit and not the GluR1 subunit. Subunit-specific trafficking of AMPARs has been known to occur and appears to be critically related to their intracellular C-terminal-binding partners. Interestingly, postsynaptic subunit-specific regulation of AMPARs is also affected by neurotransmitter release, i.e., a presynaptic effect. Because Tmub1/HOPS is found at postsynaptic sites, Tmub1/ HOPS is likely to be related to the postsynaptic complex containing GluR2 C-terminal-binding partners or GluR2, for the regulation of GluR2. GRIP, known to interact with the Cterminal site of GluR2, was coimmunoprecipitated together with GluR2 by Tmub1/HOPS from the mouse brain lysate. GRIP is known to interact with other proteins, such as kinesin, PICK1, NEEP21 
; further, it plays certain roles in the regulation of AMPAR recycling in order to modulate the level of synaptic receptors. The GluR2-GRIP complexes may associate with Tmub1/HOPS at some points of the constitutive recycling pathway. Tmub1/HOPS and GRIP were coimmunoprecipitated in HEK293 cells while they did not interact in our yeast 2-hybrid system. For the association of Tmub1/HOPS with the complexes containing GluR2 and GRIP, it may be required.