Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting.
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Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting. / Melzer, Nima; Villmann, Carmen; Becker, Kristina; Harvey, Kirsten; Harvey, Robert J; Vogel, Nico; Kluck, Christoph J; Kneussel, Matthias; Becker, Cord-Michael.
In: J BIOL CHEM, Vol. 285, No. 6, 6, 2010, p. 3730-3739.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting.
AU - Melzer, Nima
AU - Villmann, Carmen
AU - Becker, Kristina
AU - Harvey, Kirsten
AU - Harvey, Robert J
AU - Vogel, Nico
AU - Kluck, Christoph J
AU - Kneussel, Matthias
AU - Becker, Cord-Michael
PY - 2010
Y1 - 2010
N2 - The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated ion channel that mediates fast synaptic inhibition in the vertebrate central nervous system. As a member of the family of Cys-loop receptors, it assembles from five homologous subunits (GlyRalpha1-4 and -beta). Each subunit contains an extracellular ligand binding domain, four transmembrane domains (TM), and an intracellular domain, formed by the loop connecting TM3 and TM4 (TM3-4 loop). The TM3-4 loops of the subunits GlyRalpha1 and -alpha3 harbor a conserved basic motif, which is part of a potential nuclear localization signal. When tested for functionality by live cell imaging of green fluorescent protein and beta-galactosidase-tagged domain constructs, the TM3-4 loops of GlyRalpha1 and -alpha3, but not of GlyRalpha2 and -beta, exhibited nuclear sorting activity. Subunit specificity may be attributed to slight amino acid alterations in the basic motif. In yeast two-hybrid screening and GST pulldown assays, karyopherin alpha3 and alpha4 were found to interact with the TM3-4 loop, providing a molecular mechanism for the observed intracellular trafficking. These results indicate that the multifunctional basic motif of the TM3-4 loop is capable of mediating a karyopherin-dependent intracellular sorting of full-length GlyRs.
AB - The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated ion channel that mediates fast synaptic inhibition in the vertebrate central nervous system. As a member of the family of Cys-loop receptors, it assembles from five homologous subunits (GlyRalpha1-4 and -beta). Each subunit contains an extracellular ligand binding domain, four transmembrane domains (TM), and an intracellular domain, formed by the loop connecting TM3 and TM4 (TM3-4 loop). The TM3-4 loops of the subunits GlyRalpha1 and -alpha3 harbor a conserved basic motif, which is part of a potential nuclear localization signal. When tested for functionality by live cell imaging of green fluorescent protein and beta-galactosidase-tagged domain constructs, the TM3-4 loops of GlyRalpha1 and -alpha3, but not of GlyRalpha2 and -beta, exhibited nuclear sorting activity. Subunit specificity may be attributed to slight amino acid alterations in the basic motif. In yeast two-hybrid screening and GST pulldown assays, karyopherin alpha3 and alpha4 were found to interact with the TM3-4 loop, providing a molecular mechanism for the observed intracellular trafficking. These results indicate that the multifunctional basic motif of the TM3-4 loop is capable of mediating a karyopherin-dependent intracellular sorting of full-length GlyRs.
M3 - SCORING: Zeitschriftenaufsatz
VL - 285
SP - 3730
EP - 3739
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 6
M1 - 6
ER -
