Interactions among key residues regulate mammalian odorant receptor trafficking.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Xu, R; Cong, X; Zheng, Q; Xu, L; Ni, MJ; de March, CA; Matsunami, H; Golebiowski, J; Ma, M; Yu, Y

Published Date

  • July 2022

Published In

Volume / Issue

  • 36 / 7

Start / End Page

  • e22384 -

PubMed ID

  • 35639289

Pubmed Central ID

  • PMC9462447

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.202200116RR


  • eng

Conference Location

  • United States