Inhibition of XXXX -induced increase of cell-surface redistribution and activity of @entity2227 transporter type 3 by serine 465 sequence-specific peptides.

@entity2227 @entity17383 @entity535 @entity5161 @entity10185
Excitatory @entity535 transporters (EAAT) transport @entity2227 into cells to regulate @entity2227 neurotransmission and to maintain nontoxic extracellular @entity2227 levels for neurons. We showed previously that the commonly used volatile anesthetic @entity5161 increases the transporting activity of @entity17383 , the major neuronal EAAT. This effect requires a protein kinase C (PKC) a-mediated and S465-dependent @entity17383 redistribution to the plasma membrane. Thus, we hypothesize that specific peptides can be designed to block this effect. We conjugated a 10- @entity535 synthetic peptide with a sequence identical to that of @entity17383 around the S465 to a peptide that can facilitate permeation of the plasma membrane. This fusion peptide inhibited the @entity5161 -increased @entity17383 activity and redistribution to the plasma membrane in C6 cells and hippocampus. It did not affect the basal @entity17383 activity. This peptide also attenuated @entity5161 -induced increase of @entity10185 in the immunoprecipitates produced by an anti- @entity17383 antibody. A scrambled peptide that has the same @entity535 composition as the S465 sequence-specific peptide but has a random sequence did not change the effects of @entity5161 on @entity17383 . The S465 sequence-specific peptide, but not the scrambled peptide, is a good @entity10185 substrate in in vitro assay. These peptides did not affect cell viability. These results, along with our previous findings, strongly suggest that @entity10185 interacts with @entity17383 to regulate its functions. The S465 sequence-specific peptide may interrupt this interaction and is an effective inhibitor for the regulation of @entity17383 activity and trafficking by @entity10185 and @entity5161 .
