Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export

Abstract Olfactory marker protein (OMP) is a cytosolic protein expressed in mature olfactory receptor neurons (ORNs). OMP modulates cAMP signalling and regulates olfactory sensation and axonal targeting. OMP is a small soluble protein, and passive diffusion between nucleus and cytoplasm is expected....

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Main Authors: Noriyuki Nakashima, Akiko Nakashima, Kie Nakashima, Makoto Takano
Format: Article
Language:English
Published: BMC 2022-11-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-022-00973-0
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author Noriyuki Nakashima
Akiko Nakashima
Kie Nakashima
Makoto Takano
author_facet Noriyuki Nakashima
Akiko Nakashima
Kie Nakashima
Makoto Takano
author_sort Noriyuki Nakashima
collection DOAJ
description Abstract Olfactory marker protein (OMP) is a cytosolic protein expressed in mature olfactory receptor neurons (ORNs). OMP modulates cAMP signalling and regulates olfactory sensation and axonal targeting. OMP is a small soluble protein, and passive diffusion between nucleus and cytoplasm is expected. However, OMP is mostly situated in the cytosol and is only sparsely detected in the nuclei of a subset of ORNs, hypothalamic neurons and heterologously OMP-expressing cultured cells. OMP can enter the nucleus in association with transcription factors. However, how OMP is retained in the cytosol at rest is unclear. Because OMP is proposed to affect cell differentiation, it is important to understand how OMP is distributed between cytoplasm and nucleus. To elucidate the structural profile of OMP, we applied several bioinformatics methods to a multiple sequence alignment (MSA) of OMP protein sequences and ranked the evolutionarily conserved residues. In addition to the previously reported cAMP-binding domain, we identified a leucine-rich domain in the Ω-loop of OMP. We introduced mutations into the leucine-rich region and heterologously expressed the mutant OMP in HEK293T cells. Mutations into alanine increased the nuclear distribution of OMP quantified by immunocytochemistry and western blotting. Therefore, we concluded that OMP contains a leucine-rich domain important for nuclear transport.
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spelling doaj.art-5ac49646820449d29fd21d2562aa35402022-12-22T02:41:21ZengBMCMolecular Brain1756-66062022-11-0115111010.1186/s13041-022-00973-0Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear exportNoriyuki Nakashima0Akiko Nakashima1Kie Nakashima2Makoto Takano3Department of Physiology, Kurume University School of MedicineDepartment of Physiology, Kurume University School of MedicineDepartment of Physiology and Cell Biology, Kobe University School of MedicineDepartment of Physiology, Kurume University School of MedicineAbstract Olfactory marker protein (OMP) is a cytosolic protein expressed in mature olfactory receptor neurons (ORNs). OMP modulates cAMP signalling and regulates olfactory sensation and axonal targeting. OMP is a small soluble protein, and passive diffusion between nucleus and cytoplasm is expected. However, OMP is mostly situated in the cytosol and is only sparsely detected in the nuclei of a subset of ORNs, hypothalamic neurons and heterologously OMP-expressing cultured cells. OMP can enter the nucleus in association with transcription factors. However, how OMP is retained in the cytosol at rest is unclear. Because OMP is proposed to affect cell differentiation, it is important to understand how OMP is distributed between cytoplasm and nucleus. To elucidate the structural profile of OMP, we applied several bioinformatics methods to a multiple sequence alignment (MSA) of OMP protein sequences and ranked the evolutionarily conserved residues. In addition to the previously reported cAMP-binding domain, we identified a leucine-rich domain in the Ω-loop of OMP. We introduced mutations into the leucine-rich region and heterologously expressed the mutant OMP in HEK293T cells. Mutations into alanine increased the nuclear distribution of OMP quantified by immunocytochemistry and western blotting. Therefore, we concluded that OMP contains a leucine-rich domain important for nuclear transport.https://doi.org/10.1186/s13041-022-00973-0Olfactory marker protein (OMP)Hypothalamic neuronsNuclear transportNuclear export signals (NES)Leucine-rich sequenceBioinformatics
spellingShingle Noriyuki Nakashima
Akiko Nakashima
Kie Nakashima
Makoto Takano
Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
Molecular Brain
Olfactory marker protein (OMP)
Hypothalamic neurons
Nuclear transport
Nuclear export signals (NES)
Leucine-rich sequence
Bioinformatics
title Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
title_full Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
title_fullStr Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
title_full_unstemmed Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
title_short Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
title_sort olfactory marker protein contains a leucine rich domain in the ω loop important for nuclear export
topic Olfactory marker protein (OMP)
Hypothalamic neurons
Nuclear transport
Nuclear export signals (NES)
Leucine-rich sequence
Bioinformatics
url https://doi.org/10.1186/s13041-022-00973-0
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AT akikonakashima olfactorymarkerproteincontainsaleucinerichdomainintheōloopimportantfornuclearexport
AT kienakashima olfactorymarkerproteincontainsaleucinerichdomainintheōloopimportantfornuclearexport
AT makototakano olfactorymarkerproteincontainsaleucinerichdomainintheōloopimportantfornuclearexport