Tentonin 3/TMEM150C regulates glucose-stimulated insulin secretion in pancreatic β-cells

Wee, Jungwon; Pak, Sungmin; T, Kim; Hong, Gyu-Sang; Lee, Ji Seon; Nan, Jinyan; Kim, Hyungsup; Lee, Mi‐Ock; Park, Kyong Soo; Oh, Uhtaek

doi:10.1016/j.celrep.2021.110067

Cited by 14 publications

(18 citation statements)

References 56 publications

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Section: Discussionmentioning

confidence: 99%

“…In the published studies using the Tmem150c lacZ/LacZ mouse model there was no examination of LacZ activity in the cell types studied with reduced mechanosensitive current. Furthermore, proof of the success of the gene deletion appeared to be solely based on lack of immunopositive cells in Tmem150c lacZ/LacZ tissues (Wee et al, 2021; Lu et al, 2020; Hong et al, 2016). We used antibodies directed against the same epitope described in (Hong et al, 2016) to detect the protein in wild type DRG sections and in sections from Tmem150c -/- mice.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we could show that two further modes of stimulation that efficiently activate mechanosensitive channels, membrane stretch and substrate deflection also do not evoke currents in cells expressing Tmem150c (Figure 1). Using a knockout mouse model it has been claimed that loss of the TMEM150c protein is associated with a loss of mechanosensitive currents with slow inactivation kinetics in DRG neurons, nodose neurons and pancreatic β-cells (Hong et al, 2016; Lu et al, 2020; Wee et al, 2021). Here we used the same mouse model, but found that the knockout-first gene targeting strategy was associated with remaining mature wild type Tmem150c transcripts in the DRG (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Most of the evidence gathered for a functional role of TMEM150c in mediating endogenous slowly inactivating mechanosensitive currents relies on the use of the Tmem150c lacZ/LacZ mouse model (Lu et al, 2020; Hong et al, 2016; Wee et al, 2021). Here we show that Tmem150c lacZ/LacZ mice may carry a hypomorphic mutation that allows expression of wild type TMEM150c in some tissues.…”

Section: Discussionmentioning

confidence: 99%

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Lack of evidence for participation of TMEM150c/TENTONIN3 in sensory mechanotransduction

Ojeda-Alonso

Bégay

Garcia-Contreras

et al. 2022

Preprint

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The membrane protein TMEM150c has been proposed to form a mechanosensitive ion channel that is required for normal proprioceptor function. Here we examined whether expression of TMEM150c in neuroblastoma cells lacking Piezo1 is associated with the appearance of mechanosensitive currents. Using three different modes of mechanical stimuli, indentation, membrane stretch and substrate deflection we could not evoke mechanosensitive currents in cells expressing TMEM150c. We next asked if TMEM150c is necessary for the normal mechanosensitivity of cutaneous sensory neurons. We used an available mouse model in which the Tmem150c locus was disrupted through the insertion of a LacZ cassette with a splice acceptor that should lead to transcript truncation. Analysis of these mice indicated that ablation of the Tmem150c gene was not complete in sensory neurons of the dorsal root ganglia (DRG). Using a Crispr/cas9 strategy we made a second mouse model in which a large part of the Tmem150c gene was deleted and established that these Tmem150c-/- mice completely lack TMEM150c protein in the DRGs. We used an ex vivo skin nerve preparation to characterize the mechanosenstivity of mechanoreceptors and nociceptors in the glabrous skin of the Tmem150c-/- mice. We found no quantitative alterations in the physiological properties of any type of cutaneous sensory fiber in Tmem150c-/- mice. Since it has been claimed that TMEM150c is required for normal proprioceptor function we made a quantitative analysis of locomotion in Tmem150c-/- mice. Here again we found no indication that there was altered gait in Tmem150c-/- mice compared to wild type controls. In summary, we conclude that existing mouse models that have been used to investigate TMEM150c function in vivo are problematic. Furthermore, we could find no evidence that TMEM150c forms a mechanosensitive channel or that it is necessary for the normal mechanosensitivity of cutaneous sensory neurons.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lack of evidence for participation of TMEM150c/TENTONIN3 in sensory mechanotransduction

Ojeda-Alonso

Bégay

Garcia-Contreras

et al. 2022

Preprint

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“…Besides DRG and NG, TTN3 is also expressed in the murine pancreas, suggesting a role in pancreatic function. Recently, Wee et al (2021) provided additional evidence to suggest that TTN3 is a stretch-activated cation channel in pancreatic b cells, contributing to insulin secretion induced by high glucose levels and hypotonicity. Because TRPV4 and TRPV2 have been previously proposed as candidate genes for stretch-activated channels in b cells (Casas et al, 2008;Hisanaga et al, 2009), the contribution of these different channels to the stretch responses remains to be established.…”

Section: Tentonin 3/tmem150cmentioning

confidence: 99%

PIEZO channels and newcomers in the mammalian mechanosensitive ion channel family

Delmas

Parpaite

Coste

2022

Neuron

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A Hierarchical Mechanotransduction System: From Macro to Micro

Cao,

Tian,

Tian

et al. 2023

Advanced Science

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Mechanotransduction is a strictly regulated process whereby mechanical stimuli, including mechanical forces and properties, are sensed and translated into biochemical signals. Increasing data demonstrate that mechanotransduction is crucial for regulating macroscopic and microscopic dynamics and functionalities. However, the actions and mechanisms of mechanotransduction across multiple hierarchies, from molecules, subcellular structures, cells, tissues/organs, to the whole‐body level, have not been yet comprehensively documented. Herein, the biological roles and operational mechanisms of mechanotransduction from macro to micro are revisited, with a focus on the orchestrations across diverse hierarchies. The implications, applications, and challenges of mechanotransduction in human diseases are also summarized and discussed. Together, this knowledge from a hierarchical perspective has the potential to refresh insights into mechanotransduction regulation and disease pathogenesis and therapy, and ultimately revolutionize the prevention, diagnosis, and treatment of human diseases.

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Tentonin 3/TMEM150C regulates glucose-stimulated insulin secretion in pancreatic β-cells

Cited by 14 publications

References 56 publications

Lack of evidence for participation of TMEM150c/TENTONIN3 in sensory mechanotransduction

Lack of evidence for participation of TMEM150c/TENTONIN3 in sensory mechanotransduction

PIEZO channels and newcomers in the mammalian mechanosensitive ion channel family

A Hierarchical Mechanotransduction System: From Macro to Micro

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