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Role of Endosomal Sodium/Hydrogen Exchangers NHE6 and NHE9 in a Neurobiological Model of Disease
Author(s) -
Hack Anniesha,
Kondapalli Kalyan C.,
Rao Rajini
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.710.6
Subject(s) - endosome , glutamate receptor , transporter , synaptic cleft , synapse , neurotransmitter transporter , microbiology and biotechnology , neurotransmitter , neuroscience , homeostasis , chemistry , glutamatergic , receptor , biology , intracellular , biochemistry , gene
Ionic and pH gradients must be tightly regulated for many aspects of neuronal signaling and synaptic cleft homeostasis, including neurotransmitter uptake and astrocytic clearance through transporters, receptor recycling, and communication through gap junctions. Recently, several independent studies have correlated a range of neurological disorders, including autism, X‐linked mental retardation, epilepsy, attention deficit hyperactivity disorder and addiction, to mutations in a subgroup of sodium‐hydrogen exchangers, NHE6 and NHE9. These transporters are widely expressed in the brain and localize to early (NHE6) and recycling endosomes (NHE9), where they are thought to mediate the electrically silent counter transport of cations with protons to regulate luminal pH and control cargo trafficking. We have tested the hypothesis that NHE6 and NHE9 share overlapping functions in regulating intravesicular pH to control the delivery and turnover of glial specific glutamate transporters at the synapse. We have shown that isoform‐specific overexpression of NHE9 alters trafficking with increased surface expression of general (transferrin) receptors and synapse specific (glutamate) transporters. These findings provide the first insight into the neurobiological basis of NHE dysfunction. We will further elucidate the molecular mechanisms by measuring the pH of the endosomes, as well as create single and double knock down lines of NHE6 and NHE9 to demonstrate their potential overlapping functions..