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Skin elasticity is critical for maintaining skin function, yet the molecular mechanisms governing this process remain incompletely understood. Herein, we identify enkurin domain-containing protein 1 (ENKD1) as a key regulator of skin elasticity by modulating microtubule stability in basal keratinocytes. In Enkd1 knockout mice, impaired migration of basal keratinocytes results in reduced epidermal elasticity compared to wild-type controls. Mechanistically, ENKD1 localizes to the centrosome and microtubules, where its expression enhances microtubule stability. Conversely, the absence of ENKD1 destabilizes microtubules, which likely impedes keratinocyte migration and compromises epidermal elasticity. Further investigations suggest that ENKD1 exerts its effects on microtubule stability via EB1. Collectively, these findings establish ENKD1 as a pivotal regulatory factor of mammalian epidermal elasticity, providing new insights into the molecular underpinnings of skin function.
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http://dx.doi.org/10.1002/cm.70016 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
Mol Psychiatry
September 2025
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY, 14203, US.
Hyperphosphorylation of Tau and the ensuing microtubule destabilization are linked to synaptic dysfunction in Alzheimer's disease (AD). We find a marked increase of phosphorylated Tau (pTau) in cortical neurons differentiated from induced pluripotent stem cells (iPSCs) of AD patients. It is accompanied by significantly elevated expression of Serum and Glucocorticoid-regulated Kinase-1 (SGK1), which is induced by cellular stress, and Histone Deacetylase 6 (HDAC6), which deacetylates tubulin to destabilize microtubules.
View Article and Find Full Text PDFJ Thromb Haemost
September 2025
Key Laboratory of Thrombosis and Hemostasis of National Health Commission, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China; Engineering Center of Hematological Disease of Ministry of Education, Cyrus Tang Hematology Center, Collaborative Innovation
Background: Megakaryocyte (MK) fragmentation into proplatelets (PPTs) and microparticles (MKMPs) is well established, yet the mechanisms underlying MKMP generation remain unclear.
Objectives: In order to investigate the role of integrin β3 and cytoskeletal dynamics during megakaryopoiesis and explore potential therapeutic targets for thrombocytopenia.
Methods: Proplatelet formation and MKMP release were evaluated both in vivo and in vitro under integrin β3 receptor impaired environment.
Ann Anat
September 2025
Department of Biology, Faculty of Arts and Sciences, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
The Anatolian ground squirrel (Spermophilus xanthoprymnus) offers a valuable model for investigating neuroadaptive processes in the retina during hibernation. This study aimed to assess the expression of vesicular glutamate transporter 1 (VGLUT1), glutamic acid decarboxylase (GAD) isoforms GAD65 and GAD67, and microtubule-associated protein 2 (MAP2) in the retina during pre-hibernation and hibernation states. Retinal tissues were analyzed using immunohistochemistry and densitometric quantification.
View Article and Find Full Text PDFThe parasitic protozoan assembles a bipolar mitotic spindle and undergoes a closed mitosis to segregate its megabase chromosomes and mini-chromosomes through mechanisms that are distinct from its mammalian host. This parasite employs a subset of trypanosome-specific nucleus- and spindle-associated proteins (NuSAPs) to regulate mitosis, but the mechanistic roles of these proteins remain poorly understood. Here, we performed biochemical and molecular characterization of NuSAP1 and analyzed the functional interplay of NuSAP1 with its interacting and proximal proteins.
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