ArticleThe Journal of biological chemistry2011
Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion in the endosomal pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
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- Endocytotic Albumin Uptake Pathways in Human Adipose Stem Cells and Connection to Intracellular Calcium Oscillations and the Neonatal Fc receptor.Cells, tissues, organs · 2026Article
- Somatic Mutations inHypertension (Dallas, Tex. : 1979) · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- The ion channels of endomembranes.Physiological reviews · 2024Review
- S-acylation of Ca2+ transport proteins: molecular basis and functional consequences.Biochemical Society transactions · 2024Review
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- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Function of TRP channels in monocytes/macrophages.Frontiers in immunology · 2023Review
- Screening of atrial fibrillation diagnostic markers based on a GEO database chip and bioinformatics analysis.Journal of thoracic disease · 2022Article
- The evolution of organellar calcium mapping technologies.Cell calcium · 2022Review
- TheFrontiers in cell and developmental biology · 2022Article
- Mahogunin Ring Finger 1 regulates pigmentation by controlling the pH of melanosomes in melanocytes and melanoma cells.Cellular and molecular life sciences : CMLS · 2021Article
- Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation.Cardiovascular therapeutics · 2021Article
- A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles.Cellular and molecular life sciences : CMLS · 2020Review
- Transient receptor potential channels: current perspectives on evolution, structure, function and nomenclature.Proceedings. Biological sciences · 2020Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Mucolipin-3 (MCOLN3) is a pH-regulated Ca(2+) channel that localizes to the endosomal pathway. Gain-of-function mutation in MCOLN3 causes the varitint-waddler (Va) phenotype in mice, which is characterized by hearing loss, vestibular dysfunction, and coat color dilution. The Va phenotype results from a punctual mutation (A419P) in the pore region of MCOLN3 that locks the channel in an open conformation causing massive entry of Ca(2+) inside cells and inducing cell death by apoptosis. Overexpression of wild-type MCOLN3 produces severe alterations of the endosomal pathway, including enlargement and clustering of endosomes, delayed EGF receptor degradation, and impaired autophagosome maturation, thus suggesting that MCOLN3 plays an important role in the regulation of endosomal function. To understand better the physiological role of MCOLN3, we inhibited MCOLN3 function by expression of a channel-dead dominant negative mutant (458DD/KK) or by knockdown of endogenous MCOLN3. Remarkably, we found that impairment of MCOLN3 activity caused a significant accumulation of luminal Ca(2+) in endosomes. This accumulation led to severe defects in endosomal acidification as well as to increased endosomal fusion. Our findings reveal a prominent role for MCOLN3 in regulating Ca(2+) homeostasis at the endosomal pathway and confirm the importance of luminal Ca(2+) for proper acidification and membrane fusion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.