Sorting nexin 11 knockout mice exhibit enhanced thermosensing behaviour

Huang, Haowen; Li, Caiyue; Ma, Wenbo; Yin, Shikui; Zhao, Huifan; Deng, Simin; Shu, Xiaodong; Wu, Donghai; Li, Ji; Huang, Rongqi; Cheng, Na; Huang, Jufang; Li, Zhiyuan

doi:10.1111/gbb.12625

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…This finding matches well with our reports that TRPV3 is present in the lysosome of HaCaT cells 14,17,30 . Transient expression of TRPV3‐mutants (that are known to induce Olmsted syndrome , a rare genetic disorder) in HaCaT cells results in a drastic reduction in lysosomal number, distribution, and movement 14,17,31 . Based on that, we suggested that TRPV3 act as a lysosomal ion channel.…”

Section: Discussionsupporting

confidence: 91%

“…14,17,30 Transient expression of TRPV3mutants (that are known to induce Olmsted syndrome, a rare genetic disorder) in HaCaT cells results in a drastic reduction in lysosomal number, distribution, and movement. 14,17,31 Based on that, we suggested that TRPV3 act as a lysosomal ion channel. Here we show that at hyperthermic shock conditions (42°C for 2 h), macrophages lose the ability to get labelled by lysostracker red dye, suggesting that at higher temperature maintenance of low pH at lysosome is compromised.…”

Section: Discussionmentioning

confidence: 94%

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Presence of TRPV3 in macrophage lysosomes helps in skin wound healing against bacterial infection

Sahu

Goswami

2022

Experimental Dermatology

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Skin serves as the largest sensory organ that senses multiple sensory cues such as temperature, light, mechanical pressure, presence of noxious compounds, etc. [1][2][3] While the sensitivity of the skin towards certain stimuli differs from species to species, skin architecture and compositions are also highly variable in different species. Skin is the outermost tissue made of several layers of cells and it also acts as the first protective tissue for the internal organs and other tissues. 4,5 Mammalian skin represents a complex sensory as well as protective tissue. Within the skin, critical cross-talks among different cell types (such as neuro-keratinocyte interaction, neuro-immune interactions as well as keratinocyte-immune interactions) are needed for proper skin functions. Abnormalities in all these interactions may lead to skin disorders as well as the development of multiple abnormalities such as sensitization of peripheral neurons and immune system leading to more pain, itch, allergy, inflammation, hypersensitivity, etc. Such changes largely affect the physiology-related behaviours and adaptive fitness of the individual.Irrespective of architectural differences in different species, skin from all the species faces microbial attacks almost routinely.Therefore, the skin serves as the most effective barrier for all the internal organs against most of the physical, chemical, and microbial assaults. This is even more complex as both optimum body temperature and required external temperatures are not identical and differ largely from animal to animal. In a similar context, almost all living habitats ensure bacterial encounters though the extent and diversity of the bacterial groups remain uncertain. Though immune cells,

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 94%

Presence of TRPV3 in macrophage lysosomes helps in skin wound healing against bacterial infection

Sahu

Goswami

2022

Experimental Dermatology

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“…Given that, this finding suggests that the TRPV3 regulatory mechanism might have significant therapeutic and diagnostic implications in TRPV3/Ca 2+ -associated diseases ( Deng et al, 2021 ). In a different study performed in animal models, it has been shown that a vesicular trafficking protein known as SNX11 in response to temperature changes modulates mouse behavior ( Huang et al, 2020 ). Accordingly, it has been suggested that this protein may regulate thermal perception by changing the functions of TRPV3 on the plasma membrane of thermally sensitive cells ( Huang et al, 2020 ).…”

Section: Role Of Trp Channels In Health and Disease Conditionsmentioning

confidence: 99%

“…In a different study performed in animal models, it has been shown that a vesicular trafficking protein known as SNX11 in response to temperature changes modulates mouse behavior ( Huang et al, 2020 ). Accordingly, it has been suggested that this protein may regulate thermal perception by changing the functions of TRPV3 on the plasma membrane of thermally sensitive cells ( Huang et al, 2020 ). Moreover, Hung et al, in other research, revealed that TRPV1, TRPV2, and TRPV4 are functionally expressed in human esophageal squamous cells (ESCC), and the over-activation of TRPV1 and TRPV4 stimulates the proliferation and migration of these cell types.…”

Section: Role Of Trp Channels In Health and Disease Conditionsmentioning

confidence: 99%

A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies

Fallah¹,

Ahuja²,

Lin³

et al. 2022

Front. Pharmacol.

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Transient receptor potential (TRP) proteins are a large group of ion channels that control many physiological functions in our body. These channels are considered potential therapeutic drug targets for various diseases such as neurological disorders, cancers, cardiovascular disease, and many more. The Nobel Prize in Physiology/Medicine in the year 2021 was awarded to two scientists for the discovery of TRP and PIEZO ion channels. Improving our knowledge of technologies for their study is essential. In the present study, we reviewed the role of TRP channel types in the control of normal physiological functions as well as disease conditions. Also, we discussed the current and novel technologies that can be used to study these channels successfully. As such, Flux assays for detecting ionic flux through ion channels are among the core and widely used tools for screening drug compounds. Technologies based on these assays are available in fully automated high throughput set-ups and help detect changes in radiolabeled or non-radiolabeled ionic flux. Aurora’s Ion Channel Reader (ICR), which works based on label-free technology of flux assay, offers sensitive, accurate, and reproducible measurements to perform drug ranking matching with patch-clamp (gold standard) data. The non-radiolabeled trace-based flux assay coupled with the ICR detects changes in various ion types, including potassium, calcium, sodium, and chloride channels, by using appropriate tracer ions. This technology is now considered one of the very successful approaches for analyzing ion channel activity in modern drug discovery. It could be a successful approach for studying various ion channels and transporters, including the different members of the TRP family of ion channels.

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Sorting Out Sorting Nexins Functions in the Nervous System in Health and Disease

et al. 2021

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Endocytosis is a fundamental process that controls protein/lipid composition of the plasma membrane, thereby shaping cellular metabolism, sensing, adhesion, signaling, and nutrient uptake. Endocytosis is essential for the cell to adapt to its surrounding environment, and a tight regulation of the endocytic mechanisms is required to maintain cell function and survival. This is particularly significant in the central nervous system (CNS), where composition of neuronal cell surface is crucial for synaptic functioning. In fact, distinct pathologies of the CNS are tightly linked to abnormal endolysosomal function, and several genome wide association analysis (GWAS) and biochemical studies have identified intracellular trafficking regulators as genetic risk factors for such pathologies. The sorting nexins (SNXs) are a family of proteins involved in protein trafficking regulation and signaling. SNXs dysregulation occurs in patients with Alzheimer’s disease (AD), Down’s syndrome (DS), schizophrenia, ataxia and epilepsy, among others, establishing clear roles for this protein family in pathology. Interestingly, restoration of SNXs levels has been shown to trigger synaptic plasticity recovery in a DS mouse model. This review encompasses an historical and evolutionary overview of SNXs protein family, focusing on its organization, phyla conservation, and evolution throughout the development of the nervous system during speciation. We will also survey SNXs molecular interactions and highlight how defects on SNXs underlie distinct pathologies of the CNS. Ultimately, we discuss possible strategies of intervention, surveying how our knowledge about the fundamental processes regulated by SNXs can be applied to the identification of novel therapeutic avenues for SNXs-related disorders.

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Sorting nexin 11 knockout mice exhibit enhanced thermosensing behaviour

Cited by 4 publications

References 25 publications

Presence of TRPV3 in macrophage lysosomes helps in skin wound healing against bacterial infection

Presence of TRPV3 in macrophage lysosomes helps in skin wound healing against bacterial infection

A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies

Sorting Out Sorting Nexins Functions in the Nervous System in Health and Disease

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