ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2018
ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Zinc as a master regulator of intracellular organelle homeostasis.Experimental & molecular medicine · 2026Review
- ZIP8 loss impairs macrophage-mediated phagolysosomal removal of bacteria and is overcome by butyrate supplementation.Communications biology · 2026Article
- Article
- An increase of lysosomes through EGF-triggered endocytosis attenuated zinc-mediated lysosomal membrane permeabilization and neuronal cell death.Cell death & disease · 2024Article
- Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells.Journal of mammary gland biology and neoplasia · 2024Article
- The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart.The Journal of general physiology · 2023Review
- ZnT2 Is Critical for TLR4-Mediated Cytokine Expression in Colonocytes and Modulates Mucosal Inflammation in Mice.International journal of molecular sciences · 2022Article
- Review
- Alveolar cells in the mammary gland: lineage commitment and cell death.The Biochemical journal · 2022Review
- Zinc enhances autophagic flux and lysosomal function through transcription factor EB activation and V-ATPase assembly.Frontiers in cellular neuroscience · 2022Article
- Zinc Signaling in the Mammary Gland: For Better and for Worse.Biomedicines · 2021Review
- Membrane transport proteins in melanosomes: Regulation of ions for pigmentation.Biochimica et biophysica acta. Biomembranes · 2020Review
- Functions of Lysosomes in Mammalian Female Reproductive System.Reproductive and developmental medicine · 2020Article
- HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells.Frontiers in immunology · 2020Article
- Lysosomal size matters.Traffic (Copenhagen, Denmark) · 2020Review
- Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysfunction in women with common genetic variants in SLC30A2.Scientific reports · 2019Article
- Diffuse optical spectroscopic imaging for the investigation of human lactation physiology: a case study on mammary involution.Journal of biomedical optics · 2019Article
- ZnT2 is an electroneutral proton-coupled vesicular antiporter displaying an apparent stoichiometry of two protons per zinc ion.PLoS computational biology · 2019Article
- Lipophagy and Alcohol-Induced Fatty Liver.Frontiers in pharmacology · 2019Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Mammary gland involution, a tightly regulated process of tissue remodeling by which a lactating mammary gland reverts to the prepregnant state, is characterized by the most profound example of regulated epithelial cell death in normal tissue. Defects in the execution of involution are associated with lactation failure and breast cancer. Initiation of mammary gland involution requires upregulation of lysosome biogenesis and acidification to activate lysosome-mediated cell death; however, specific mediators of this initial phase of involution are not well described. Zinc transporter 2 [ZnT2 ( SLC30A2)] has been implicated in lysosome biogenesis and lysosome-mediated cell death during involution; however, the direct role of ZnT2 in this process has not been elucidated. Here we showed that ZnT2-null mice had impaired alveolar regression and reduced activation of the involution marker phosphorylated Stat3, indicating insufficient initiation of mammary gland remodeling during involution. Moreover, we found that the loss of ZnT2 inhibited assembly of the proton transporter vacuolar ATPase on lysosomes, thereby decreasing lysosome abundance and size. Studies in cultured mammary epithelial cells revealed that while the involution signal TNFα promoted lysosome biogenesis and acidification, attenuation of ZnT2 impaired the lysosome response to this involution signal, which was not a consequence of cytoplasmic Zn accumulation. Our findings establish ZnT2 as a novel regulator of vacuolar ATPase assembly, driving lysosome biogenesis, acidification, and tissue remodeling during the initiation of mammary gland involution.
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