An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells

Hironori Saito; Masato Kimura; Atsushi Inanobe; Toru Ohe; Yoshihisa Kurachi

doi:10.1016/s0006-291x(02)00899-9

An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells

Biochem Biophys Res Commun. 2002 Aug 23;296(3):523-9. doi: 10.1016/s0006-291x(02)00899-9.

Authors

Hironori Saito¹, Masato Kimura, Atsushi Inanobe, Toru Ohe, Yoshihisa Kurachi

Affiliation

¹ Department of Pharmacology II, Graduate School of Medicine, Osaka University, Suita, Yamada-oka 2-2, Osaka 565-0871, Japan.

PMID: 12176012
DOI: 10.1016/s0006-291x(02)00899-9

Abstract

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.

MeSH terms

Alternative Splicing
Amino Acid Sequence
Animals
Antibodies / immunology
Binding Sites
Carrier Proteins / chemistry*
Carrier Proteins / genetics
Carrier Proteins / immunology
Carrier Proteins / physiology*
Cell Line
Cloning, Molecular
Homer Scaffolding Proteins
Humans
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Muscles / metabolism
Neuropeptides / chemistry*
Neuropeptides / genetics
Neuropeptides / immunology
Neuropeptides / physiology*
Proline / metabolism
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / physiology
Protein Transport
RNA, Messenger / biosynthesis
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / chemistry
Receptors, Metabotropic Glutamate / metabolism*
Sequence Alignment

Substances

Antibodies
Carrier Proteins
GRM5 protein, human
Grm5 protein, mouse
HOMER1 protein, human
Homer Scaffolding Proteins
Homer1 protein, mouse
Neuropeptides
Protein Isoforms
RNA, Messenger
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1
Proline