title: The transmembrane transporter domain of glutamate transporters is a process tip localizer.
abstract: Glutamate transporters in the central nervous system remove glutamate released from neurons to terminate the signal. These transporters localize to astrocyte process tips approaching neuronal synapses. The mechanisms underlying the localization of glutamate transporters to these processes, however, are not known. In this study, we demonstrate that the trimeric transmembrane transporter domain fragment of glutamate transporters, lacking both N- and C-terminal cytoplasmic regions, localized to filopodia tips. This is a common property of trimeric transporters including a neutral amino acid transporter ASCT1. Astrocyte specific proteins are not required for the filopodia tip localization. An extracellular loop at the centre of the 4(th) transmembrane helices, unique for metazoans, is required for the localization. Moreover, a C186S mutation at the 4(th) transmembrane region of EAAT1, found in episodic ataxia patients, significantly decreased its process tip localization. The transmembrane transporter domain fragments of glutamate transporters also localized to astrocyte process tips in cultured hippocampal slice. These results indicate that the transmembrane transporter domain of glutamate transporters have an additional function as a sorting signal to process tips.
authors.affiliation: Department of Pharmacology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Mariko Kato
authors.initials: MK
authors.lastname: Hayashi
authors.affiliation: Department of Pharmacology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yasui
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001259:Ataxia / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D027322:Amino Acid Transport System X-AG; D020033:Protein Isoforms