Interactions among key residues regulate mammalian odorant receptor trafficking.
Odorant receptors (ORs) expressed in mammalian olfactory sensory neurons are essential for the sense of smell. However, structure-function studies of many ORs are hampered by unsuccessful heterologous expression. To understand and eventually overcome this bottleneck, we performed heterologous expression and functional assays of over 80 OR variants and chimeras. Combined with literature data and machine learning, we found that the transmembrane domain 4 (TM4) and its interactions with neighbor residues are important for OR functional expression. The data highlight critical roles of T4.62 therein. ORs that fail to reach the cell membrane can be rescued by modifications in TM4. Consequently, such modifications in MOR256-3 (Olfr124) also alter OR responses to odorants. T1614.62 P causes the retention of MOR256-3 in the endoplasmic reticulum (ER), while T1614.62 P/T1484.49 A reverses the retention and makes receptor trafficking to cell membrane. This study offers new clues toward wide-range functional studies of mammalian ORs.
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Related Subject Headings
- Smell
- Receptors, Odorant
- Odorants
- Mammals
- Cell Membrane
- Biochemistry & Molecular Biology
- Animals
- 3208 Medical physiology
- 3101 Biochemistry and cell biology
- 1116 Medical Physiology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Smell
- Receptors, Odorant
- Odorants
- Mammals
- Cell Membrane
- Biochemistry & Molecular Biology
- Animals
- 3208 Medical physiology
- 3101 Biochemistry and cell biology
- 1116 Medical Physiology