-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Written by | Yiming
In order to accurately and quickly identify odor molecules in the environment, the olfactory sensory neurons (olfactory sensory neurons) of the main olfactory epithelial cells (MOEs) of mice are mice More than 1000 olfactory receptors are expressed [1].
In the process of odor recognition, "receptors and neurons" and "receptors and olfactory globules" follow the principle of one-to-one correspondence of a radish and a pit, that is, only one olfactory receptor is expressed on each olfactory neuron, and neurons expressing the same olfactory receptor are projected onto the same olfactory globulus, which are the two key characteristics
of changing from odor detection to odor perception.
The regulatory process of accurate odor perception and the supervision mechanism of the strict correspondence between olfactory receptors, neurons and olfactory globuli, the molecular biological basis of which is not clear
.
Recently, the Stavros Lomvardas research group at Columbia University published an article in Cell ER stress transforms random olfactory receptor choice into axon-targeting precision The study found that the PERK arm in the unfolded protein response (UPR) plays an important role in regulating the aggregation of olfactory glomerules corresponding to similar olfactory neurons and the specific projection of olfactory neurons to the olfactory globulus, and that nuances in olfactory receptor sequences lead to varying degrees of ER stress (ERS) during the development of olfactory sensory neurons The transcription factor Ddit3 is a key effector of PERK signaling, which further regulates the transcription of axonal guide and cell adhesion genes, and realizes the precise regulation
of olfactory neuronal axon targeting.
Olfactory receptors translate in the endoplasmic reticulum (ER) and then activate PERK signaling and expression
of Atf5 transcription factors induced by PERK.
The researchers hypothesized that if the identity of olfactory sensory neurons is mapped to axon-targeted guidance through different patterns of ERS, then PERK signaling must change
with the identity of olfactory receptors.
To verify this, the study replaced the coding sequence
of Atf5 with iRFPp2a-Cre.
Atf5 is a PERK-induced transcription factor (TF) that is transcribed
in olfactory sensory neuron lines.
Through immunofluorescence (IF), flow cytometry sorting, and RNA-seq experiments, the researchers found that the reporting system could be used to quantitatively assess
the relationship between olfactory sensory neuron properties and PERK signaling.
To test whether the ERS patterns of different olfactory sensory neurons differed, the researchers mapped the ERS trajectories
of all olfactory sensory neurons through flow cytometry sorting.
Two groups of olfactory sensory neurons were defined, and the 25% of the olfactory sensory neurons with the highest and lowest iRFP intensities were screened out, and then RNA-seq
was performed.
The results showed that high ERS olfactory sensory neurons expressed UPR-related genes at higher levels than cells with low ERS, confirming that differences in reported intensity represent UPR differences
.
The researchers observed extensive changes in ERS in each region, suggesting that olfactory receptor and regional properties correlated
with overall ERS levels in developing olfactory sensory neurons.
To explore how olfactory receptor protein sequences affect UPR, the researchers found through multiple sequence alignment (MSA) and principal coordinate analysis (PCoA) that an olfactory receptor's ability to induce ERS is largely encoded by its primary amino acid sequence
。 Olfactory receptors with similar sequences induce similar levels of ERS, while amino acid substitution induces axon-directed shifts that follow predicted changes in ERS In order to explore the link between UPR and olfactory sensory neuronal targeting, the researchers explored whether differences in ERS were related to changes in
the expression of axonal guide genes.
By scRNA-seq analysis, ERS was found to be associated with
differences in the expression of many axon-guided molecules.
A slight decrease in PERK signal may result in axonal targeted transfer without disrupting axon cohesion
.
This suggests that axonal guidance responds to both enhanced and weakened UPR regulation, and that changes in ERS affect molecular discrimination and isolation
of olfactory sensory neuronal axons.
In addition, the researchers further confirmed the regulator effect
of Ddit3 by analyzing the scRNA-seq data and further experimental verification.
In summary, UPR plays the function
of guiding axon wiring during the establishment of neural circuits.
PERK combined with specific olfactory receptors to determine the identity characteristics of olfactory neurons, and olfactory receptor-induced ERS regulated the level of DDIT3, further regulating multiple molecular changes
at the transcriptome level within cells.
At the same time, the ability of an olfactory receptor to induce ERS is closely related
to the amino acid sequence.
The significance of UPR in the process of establishing neural circuits to regulate axon targeting is:
first, the participation of UPR pathways ensures that smell-related neural circuits can be formed without odor.
For example, during embryonic development or in cases of sensory deprivation;
Second, the amino acid sequence information of the olfactory receptor induces the degree of correspondence of ERS, and this genetic stability corresponds to ER signaling, explaining how this olfactory neural circuit remains stable
in a world with complex and changeable sensations.
Why did organisms evolve such complex mechanisms for olfactory receptor recognition of odors? The evolution of novel olfactory receptor proteins is limited to having to co-evolve with functional neural circuits, and with the involvement of the UPR pathway, PERK can capture subtle amino acid changes, and ERS may be able to help novel olfactory receptors, ensuring that any new sensory "channel" is automatically embodied in
a new olfactory globulus.
The limitations of this study include: 1) the mechanism by which these amino acid residues control ERS has not been explored; 2) In the process of cell sorting, only 25% of the situation before and after was paid attention to; 3) Regarding the relationship between ERS and axon guidance, it cannot be ruled out that PERK signals guide axons through mechanisms unrelated to Ddit3; 4) The study analyzes the causal relationship between olfactory receptor identity, ERS and axon guidance based on calculation, which requires further experimental verification; 5) The study only explored the effect of PERK signaling on the period of
olfactory neural circuit establishment.
Original link: https://doi.
org/10.
1016/j.
cell.
2022.
08.
025
Plate maker: Eleven
In order to accurately and quickly identify odor molecules in the environment, the olfactory sensory neurons (olfactory sensory neurons) of the main olfactory epithelial cells (MOEs) of mice are mice More than 1000 olfactory receptors are expressed [1].
In the process of odor recognition, "receptors and neurons" and "receptors and olfactory globules" follow the principle of one-to-one correspondence of a radish and a pit, that is, only one olfactory receptor is expressed on each olfactory neuron, and neurons expressing the same olfactory receptor are projected onto the same olfactory globulus, which are the two key characteristics
of changing from odor detection to odor perception.
The regulatory process of accurate odor perception and the supervision mechanism of the strict correspondence between olfactory receptors, neurons and olfactory globuli, the molecular biological basis of which is not clear
.
Recently, the Stavros Lomvardas research group at Columbia University published an article in Cell ER stress transforms random olfactory receptor choice into axon-targeting precision The study found that the PERK arm in the unfolded protein response (UPR) plays an important role in regulating the aggregation of olfactory glomerules corresponding to similar olfactory neurons and the specific projection of olfactory neurons to the olfactory globulus, and that nuances in olfactory receptor sequences lead to varying degrees of ER stress (ERS) during the development of olfactory sensory neurons The transcription factor Ddit3 is a key effector of PERK signaling, which further regulates the transcription of axonal guide and cell adhesion genes, and realizes the precise regulation
of olfactory neuronal axon targeting.
Olfactory receptors translate in the endoplasmic reticulum (ER) and then activate PERK signaling and expression
of Atf5 transcription factors induced by PERK.
The researchers hypothesized that if the identity of olfactory sensory neurons is mapped to axon-targeted guidance through different patterns of ERS, then PERK signaling must change
with the identity of olfactory receptors.
To verify this, the study replaced the coding sequence
of Atf5 with iRFPp2a-Cre.
Atf5 is a PERK-induced transcription factor (TF) that is transcribed
in olfactory sensory neuron lines.
Through immunofluorescence (IF), flow cytometry sorting, and RNA-seq experiments, the researchers found that the reporting system could be used to quantitatively assess
the relationship between olfactory sensory neuron properties and PERK signaling.
To test whether the ERS patterns of different olfactory sensory neurons differed, the researchers mapped the ERS trajectories
of all olfactory sensory neurons through flow cytometry sorting.
Two groups of olfactory sensory neurons were defined, and the 25% of the olfactory sensory neurons with the highest and lowest iRFP intensities were screened out, and then RNA-seq
was performed.
The results showed that high ERS olfactory sensory neurons expressed UPR-related genes at higher levels than cells with low ERS, confirming that differences in reported intensity represent UPR differences
.
The researchers observed extensive changes in ERS in each region, suggesting that olfactory receptor and regional properties correlated
with overall ERS levels in developing olfactory sensory neurons.
To explore how olfactory receptor protein sequences affect UPR, the researchers found through multiple sequence alignment (MSA) and principal coordinate analysis (PCoA) that an olfactory receptor's ability to induce ERS is largely encoded by its primary amino acid sequence
。 Olfactory receptors with similar sequences induce similar levels of ERS, while amino acid substitution induces axon-directed shifts that follow predicted changes in ERS In order to explore the link between UPR and olfactory sensory neuronal targeting, the researchers explored whether differences in ERS were related to changes in
the expression of axonal guide genes.
By scRNA-seq analysis, ERS was found to be associated with
differences in the expression of many axon-guided molecules.
A slight decrease in PERK signal may result in axonal targeted transfer without disrupting axon cohesion
.
This suggests that axonal guidance responds to both enhanced and weakened UPR regulation, and that changes in ERS affect molecular discrimination and isolation
of olfactory sensory neuronal axons.
In addition, the researchers further confirmed the regulator effect
of Ddit3 by analyzing the scRNA-seq data and further experimental verification.
In summary, UPR plays the function
of guiding axon wiring during the establishment of neural circuits.
PERK combined with specific olfactory receptors to determine the identity characteristics of olfactory neurons, and olfactory receptor-induced ERS regulated the level of DDIT3, further regulating multiple molecular changes
at the transcriptome level within cells.
At the same time, the ability of an olfactory receptor to induce ERS is closely related
to the amino acid sequence.
The significance of UPR in the process of establishing neural circuits to regulate axon targeting is:
first, the participation of UPR pathways ensures that smell-related neural circuits can be formed without odor.
For example, during embryonic development or in cases of sensory deprivation;
Second, the amino acid sequence information of the olfactory receptor induces the degree of correspondence of ERS, and this genetic stability corresponds to ER signaling, explaining how this olfactory neural circuit remains stable
in a world with complex and changeable sensations.
Why did organisms evolve such complex mechanisms for olfactory receptor recognition of odors? The evolution of novel olfactory receptor proteins is limited to having to co-evolve with functional neural circuits, and with the involvement of the UPR pathway, PERK can capture subtle amino acid changes, and ERS may be able to help novel olfactory receptors, ensuring that any new sensory "channel" is automatically embodied in
a new olfactory globulus.
The limitations of this study include: 1) the mechanism by which these amino acid residues control ERS has not been explored; 2) In the process of cell sorting, only 25% of the situation before and after was paid attention to; 3) Regarding the relationship between ERS and axon guidance, it cannot be ruled out that PERK signals guide axons through mechanisms unrelated to Ddit3; 4) The study analyzes the causal relationship between olfactory receptor identity, ERS and axon guidance based on calculation, which requires further experimental verification; 5) The study only explored the effect of PERK signaling on the period of
olfactory neural circuit establishment.
Original link: https://doi.
org/10.
1016/j.
cell.
2022.
08.
025
Plate maker: Eleven
References
1-Buck, L.
, and Axel, R.
(1991).
A novel multigene family may encode odorant receptors: a molecular basis for odor recognition.
Cell 65, 175–187
Reprint instructions
【Original article】BioArt original article, welcome to share by individuals, reproduction is prohibited without permission, the copyright of all works published is owned by BioArt
.
BioArt reserves all statutory rights and violators will be prosecuted
.
