Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Pleiotropy01:33

Pleiotropy

43.1K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.1K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

5.9K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Notch Signaling Pathway03:14

Notch Signaling Pathway

6.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.3K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

4.9K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
4.9K
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

2.8K
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Association of menopausal type and hormone therapy with headache in a large Taiwanese cohort.

Maturitas·2026
Same author

DDR1 Modulates Cytoskeletal Remodeling and Podosome Formation in Renal Fibroblasts.

International journal of molecular sciences·2026
Same author

Loss-of-Function (G603R) Lrp10 Fails to Downregulate mRNA of Pathologic α-Synuclein and Causes Neurodegeneration of Substantia Nigra Dopaminergic Cells in Parkinson's Disease Knockin Mice.

Neurochemical research·2026
Same author

Lrp10 insufficiency upregulates mRNA and protein of neurotoxic α-synuclein and causes degeneration of substantia nigra dopaminergic neurons in heterozygous or homozygous Lrp10 knockout mice.

Neurochemistry international·2026
Same author

Deletion of mitochondrial calcium uniporter enhances calcium signals by slowing calcium clearance and triggers adaptive transcriptomic remodeling.

The Journal of biological chemistry·2026
Same author

Baseline Depressive Symptoms and Heart Rate Variability Indices Predict HRV Biofeedback Outcomes in Young Adults with Depression.

Applied psychophysiology and biofeedback·2026
Same journal

Circulating MYOM3 fragments reflect disease severity and therapeutic efficacy in tubular aggregate myopathy and Stormorken syndrome.

Human molecular genetics·2026
Same journal

The FVB-nmd SMARD1 mouse presents with early respiratory deficits and pathology that significantly impact lifespan.

Human molecular genetics·2026
Same journal

Utrophin requires α-Syntrophin to maintain neuromuscular junction integrity in mdx mice.

Human molecular genetics·2026
Same journal

A novel gene ACTRT3 mutations induce sperm malformations and fertilization failure via Acrosomal ultrastructural defects.

Human molecular genetics·2026
Same journal

Nucleic acid-based therapeutic strategies for modulator-refractory cystic fibrosis-causing variants.

Human molecular genetics·2026
Same journal

Evidence that disruption of Discoidin domain receptor 2 contributes to palate malformations through effects on the extracellular matrix.

Human molecular genetics·2026
See all related articles

Related Experiment Video

Updated: Jan 6, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
10:45

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement

Published on: July 26, 2017

10.6K

Single-nucleotide polymorphisms in Orai1 associated with atopic dermatitis inhibit protein turnover, decrease calcium

Yi-Chun Yeh1, Yu-Ping Lin1, Holger Kramer2

  • 1Department of Physiology, Anatomy and Genetics, Parks Road, Oxford, OX1 3PT UK.

Human Molecular Genetics
|October 11, 2019
PubMed
Summary
This summary is machine-generated.

Single-nucleotide polymorphisms (SNPs) in Orai1 channels are linked to atopic dermatitis. These Orai1-SNPs exhibit slower turnover and altered recycling, impacting calcium signaling and gene expression, offering new therapeutic targets.

More Related Videos

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

10.5K
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

5.0K

Related Experiment Videos

Last Updated: Jan 6, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
10:45

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement

Published on: July 26, 2017

10.6K
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

10.5K
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

5.0K

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Loss-of-function mutations in Orai1 Ca2+ channels cause severe combined immunodeficiency, autoimmunity, and developmental defects.
  • Two single-nucleotide polymorphisms (SNPs) in Orai1, located in the second extracellular loop, are associated with atopic dermatitis, but their functional impact remains unclear.

Purpose of the Study:

  • To investigate the functional consequences of Orai1-SNPs on Orai1 channel trafficking, calcium signaling, and cellular function.
  • To elucidate the mechanisms underlying the altered turnover and localization of Orai1-SNPs.

Main Methods:

  • Utilized cell-based assays to compare the turnover and localization of wild-type Orai1 and Orai1-SNPs.
  • Investigated the role of flotillin, Rab proteins (Rab 7 and Rab 11), and Arf6 in Orai1 channel trafficking.
  • Analyzed the impact of altered Orai1 localization on calcium influx and gene expression.

Main Results:

  • Orai1-SNPs exhibit significantly slower turnover and increased abundance in the plasma membrane compared to wild-type Orai1.
  • Flotillin mediates the endocytotic recycling of Orai1 channels.
  • Wild-type Orai1 undergoes lysosomal degradation via late endosomes, while Orai1-SNPs are directed to recycling endosomes and escape degradation through pH-sensitive interactions with flotillin.
  • Increased membrane Orai1-SNP levels disrupt Orai1-STIM stoichiometry, inhibiting Ca2+ entry and Ca2+-dependent gene expression.

Conclusions:

  • Orai1-SNPs escape normal degradation pathways, leading to altered calcium channel function.
  • pH-sensitive interactions involving extracellular loops of Orai1 regulate its turnover and trafficking.
  • The aberrant trafficking and signaling of Orai1-SNPs provide novel therapeutic targets for atopic dermatitis.