How do we taste sour? That’s honestly not a question that I’d really thought about before but Dr. Emily Liman detailed her elegant answer to this question in the Symposium on Sensational Membrane Proteins. Turns out, humans can detect five basic tastes: bitter, sour, sweet, salty, and umami. FYI: a quick Google search informed me that umami is a savory or meaty flavor. Various types of specially localized cells in the tongue are able to detect these tastes and many of the specific protein receptors that mediate these processes were previously identified – except for the elusive sour sensing protein.
Dr. Liman described the heroic efforts required to identify and understand how this protein may work. First, the Taste Receptor Cells (TCR) that are responsible for sour sensing were identified (i.e., Type III TCRs) and the transcriptome of these cells were compared to other TCRs. Protein sequences that were enriched within the type III TCRs were investigated for sour sensing. So what exactly is sour sensing activity? Unsurprisingly, the common factor between sour tasting compounds is that they are acidic. After a lot of functional assays, they identified the protein Otopetrin 1 (Otop1) as the proton channel required for sour sensing in type III TCRs.
They even confirmed that mice lacking Otop1 exhibited lowered reactions to mild acid (Teng, et al., Cellular and Neural Responses to Sour Stimuli Require the Proton Channel Otop1, Current Biology (2019) 29, 3647-3656). When I read that finding, I paused and chuckled – what’s the experimental read out in determining a mouse’s reaction to different tastes? I don’t do any mouse model work and thought I’d dig into this. I imagined scientists watching the facial expressions of a little mouse and waiting to see if it scrunched up after exposure to sour taste. After all, that’s what I do after tasting limes! Turns out, that’s essentially how it works – the chorda tympani is a facial nerve that originates from the taste bud and these experiments monitor chorda tympani stimulation in response to various acidic stimuli. Of course, it’s in a more quantitative and statistical manner than what I originally imagined.
The Liman lab has gone on to complement their functional assays with a structural biology approach via cryo-EM. The structure of zebrafish Otop1 in lipid nanodiscs revealed a dimeric state with a central tunnel occluded by cholesterol (Saotome, et al., Structures of the otopetrin proton channels Otop1 and Otop3, NSMB (2019) 26, 518-525). It seems like the work is now cut out for future understanding of how the Otop1 proton channel function relates to its structural organization.
On a slightly related note, for the enjoyment of your taste buds, I’d suggest trying the tacos at Rockin’ Baja Lobster. And maybe get a lime with your margarita to give your Otop1 some work to do.