The endoplasmic reticulum exit of glutamate transporter is regulated by the inducible mammalian Yip6b/GTRAP3-18 protein.
GTRAP3-18 interacts with and reduces the activity of the neuronal specific Na(+)/K(+) glutamate transporter, EAAC1 both in vitro and in vivo. GTRAP3-18 and the related isoform, JM4, are distant relatives of the Rab GTPase-interacting factor PRA1, and share a topology of four transmembrane domains and cytosolic termini. GTRAP3-18 and JM4 are resident endoplasmic reticulum (ER) proteins. The physiological role of GTRAP3-18 is poorly understood. We demonstrate for the first time that GTRAP3-18 is a regulator of ER protein trafficking. Expression of GTRAP3-18 delays the ER exit of EAAC1, as well as other members of the excitatory amino acid transporter family. GTRAP3-18 uses hydrophobic domain interactions in the ER membrane to self-associate and cytoplasmic interactions at the C terminus to regulate trafficking. The features of GTRAP3-18 activity are consistent with recent phylogenic sequence analyses suggesting GTRAP3-18 and JM4 be reclassified as mammalian isoforms of the yeast protein family Yip, Yip6b, and Yip6a, respectively.
Ruggiero
Alicia M
AM
Department of Neuroscience, Johns Hopkins University, 625 N. Wolfe Street, Baltimore, MD 21287, USA.
Liu
Yiting
Y
Vidensky
Svetlana
S
Maier
Susanne
S
Jung
Elizabeth
E
Farhan
Hesso
H
Robinson
Michael B
MB
Sitte
Harald H
HH
Rothstein
Jeffrey D
JD
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006360:Heat-Shock Proteins; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein
C464502:Arl6ip5 protein, mouse; D002352:Carrier Proteins; D050580:Excitatory Amino Acid Transporter 3; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C499863:PRAF2 protein, human; D020033:Protein Isoforms; C493400:SLC1A1 protein, human; C493399:Slc1a1 protein, mouse