Sensory Systems of the African Naked Mole-Rat

Vice, Emily N.; Lagestee, Samantha; Browe, Brigitte; Deb, Deblina; Smith, Ewan St. John; Park, Thomas J.

doi:10.1007/978-3-030-65943-1_5

Cited by 9 publications

(2 citation statements)

References 68 publications

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“…For example, birds are known to be less sensitive to sour taste, while they need to avoid ingesting NH 4 Cl present in their excrement. Interestingly, naked mole rats which live in a high ammonium environment can detect but do not avoid ammonia fumes 52 , likely due to the inactivation of more general nociceptive signaling; compared with mice their taste system is less sensitive to acids but if they are also less sensitive to the taste of NH 4 Cl is not known 53 .…”

Section: Discussionmentioning

confidence: 99%

The proton channel OTOP1 is a sensor for the taste of ammonium chloride

Liang,

Wilson,

Teng

et al. 2023

Nat Commun

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Ammonium (NH4+), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NH4Cl). Extracellular NH4Cl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NH4Cl relative to acid stimuli. Taste responses to NH4Cl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1−/− mouse strain. Behavioral aversion of mice to NH4Cl, reduced in Skn-1a−/− mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NH4Cl and a previously undescribed channel activation mechanism.

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Section: Discussionmentioning

confidence: 99%

The proton channel OTOP1 is a sensor for the taste of ammonium chloride

Liang,

Wilson,

Teng

et al. 2023

Nat Commun

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“…Although naked mole‐rats ( Heterocephalus glaber ) were first described more than 150 years ago (Rüppell, 1842 ) it is only over the last 40 years that scientists have begun to dig deeply into the many facets of their unusual biology (Buffenstein, Park & Holmes, 2021 ). The naked mole‐rat has not only garnered attention for being a eusocial mammal (Jarvis, 1981 ; Holmes & Goldman, 2021 ), highly specialised for life underground through sensory (Lewin et al ., 2021 ; Vice et al ., 2021 ) and ecophysiological adaptations (Buffenstein & Craft, 2021 ), but it has also been used in biomedical studies. These include research on pain (Park et al ., 2008 ; Eigenbrod et al ., 2019 ) hypoxia tolerance (Larson et al ., 2014 ; Park et al ., 2017 , 2021 ; Ivy et al ., 2020 ), cardiac function (Grimes et al ., 2014 b ), cancer (Tian et al ., 2013 ; Miyawaki et al ., 2016 ; Taylor, Milone & Rodriguez, 2017 ; Seluanov et al ., 2018 ; Shepard & Kissil, 2020 ; Delaney, Imai & Buffenstein, 2021 ), neuropeptidergic control of reproduction and behaviour (Coen et al ., 2021 ), and ageing (Buffenstein, 2005 ; Lewis & Buffenstein, 2016 ; Ruby, Smith & Buffenstein, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole‐rat biology

et al. 2021

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The naked mole‐rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled ‘Surprisingly long survival of premature conclusions about naked mole‐rat biology’ described 28 ‘myths’ which, those authors claimed, are a ‘perpetuation of beautiful, but falsified, hypotheses’ and impede our understanding of this enigmatic mammal. Here, we re‐examine each of these ‘myths’ based on evidence published in the scientific literature. Following Braude et al., we argue that these ‘myths’ fall into four main categories: (i) ‘myths’ that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) ‘myths’ that are based on incomplete understanding, where more evidence is clearly needed; (iii) ‘myths’ where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) ‘myths’ where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term ‘myth’ is particularly inappropriate when applied to competing, evidence‐based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole‐rat biology and attempt to clarify some of these misconceptions.

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