An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells.
Homer proteins bind to a proline-rich region of the group I metabotropic glutamate receptors (mGluRs) and control their expression and localization at the excitatory postsynaptic density. We isolated a novel isoform of Homer1, Homer1d, from a mouse heart cDNA library. Its N-terminal end of 18 amino acids was unique among Homer1 variants (Homer1a-d), while the remainder of Homer1d was identical to that of Homer1b. To clarify the function of its N-terminus, we expressed Homer1b and 1d in the presence and absence of mGluR5b in HEK293T cells. When expressed alone, both Homer proteins were distributed diffusely in the cytoplasm and mGluR5b was on the plasma membrane (PM). When co-expressed, Homer1d and mGluR5b were co-localized on the PM, while Homer1b and mGluR5b were retained in the endoplasmic reticulum (ER). Both Homer proteins bound to mGluR5b in vitro. Therefore, the N-terminal portion of Homer1d may facilitate trafficking of Homer1-mGluR5 complex from the ER to the PM.
Saito
Hironori
H
Department of Pharmacology II, Graduate School of Medicine, Osaka University, Suita, Yamada-oka 2-2, Osaka 565-0871, Japan.
Kimura
Masato
M
Inanobe
Atsushi
A
Ohe
Toru
T
Kurachi
Yoshihisa
Y
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D000072233:Homer Scaffolding Proteins; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011392:Proline / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
D000906:Antibodies; D002352:Carrier Proteins; C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; C000606614:HOMER1 protein, human; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; D009479:Neuropeptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D011392:Proline