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In the present study, we generated and characterized a splice site-specific monoclonal antibody that selectively detects the calcineurin-binding dynamin1 splice variant dynamin1xb. Calcineurin is a Ca-regulated phosphatase that enhances dynamin1 activity and is an important Ca-sensing mediator of homeostatic synaptic plasticity in neurons. Using this dynamin1xb-specific antibody, we found dynamin1xb highly enriched in synapses of all analyzed brain regions. In photoreceptor ribbon synapses, dynamin1xb was enriched in close vicinity to the synaptic ribbon in a manner indicative of a peri-active zone immunolabeling. Interestingly, in dark-adapted mice we observed an enhanced and selective enrichment of dynamin1xb in both synaptic layers of the retina in comparison to light-adapted mice. This could be due to an illumination-dependent recruitment of dynamin1xb to retinal synapses and/or due to a darkness-induced increase of dynamin1xb biosynthesis. These latter findings indicate that dynamin1xb is part of a versatile and highly adjustable, activity-regulated endocytic synaptic machinery.
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http://dx.doi.org/10.3389/fnmol.2017.00230 | DOI Listing |
Nucleic Acids Res
September 2025
Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China.
EZH2 catalyzes H3K27me3 and is essential for embryonic development. Although multiple EZH2 variants have been identified, the functional implications and physiological significance of its heterogeneity remain unclear. Here, we revealed that conserved cryptic splice sites generated two EZH2 variants with (EZH2A) or without (EZH2B) a 27-nt region, coding for a 9-aa segment.
View Article and Find Full Text PDFFront Genet
August 2025
Medical School, Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Background: Stickler syndrome (STL) is a group of related connective tissue disorders characterized by heterogeneous clinical presentations with varying degrees of orofacial, ocular, skeletal, and auditory abnormalities. However, this condition is difficult to diagnose on the basis of clinical features because of phenotypic variability. Thus, expanding the variant spectrum of this disease will aid in achieving a firm definitive diagnosis of STL.
View Article and Find Full Text PDFRecursive splice sites are rare motifs postulated to facilitate splicing across massive introns and shape isoform diversity, especially for long, brain-expressed genes. The necessity of this unique mechanism remains unsubstantiated, as does the role of recursive splicing (RS) in human disease. From analyses of rare copy number variants (CNVs) from almost one million individuals, we previously identified large, heterozygous deletions eliminating an RS site (RS1) in the first intron of that conferred substantial risk for attention deficit hyperactivity disorder (ADHD) and other neurobehavioral traits.
View Article and Find Full Text PDFBlood Vessel Thromb Hemost
August 2025
Hematology, Thrombosis and Hemostasis Research Program, Versiti Blood Research Institute, Wauwatosa, WI.
Unopposed platelet activation can be associated with pathologic thrombosis. An intact growth arrest-specific gene 6 (GAS6)/Mer receptor tyrosine kinase (MERTK) signaling pathway contributes importantly to potentiating platelet activation triggered by molecular agonists ex vivo and thrombus stabilization in vivo. We describe, herein, the inhibition of platelet function and stable thrombus formation conferred by iMer, a naturally occurring MERTK splice variant, that acts as a GAS6 decoy receptor and decreases phosphorylation of MERTK.
View Article and Find Full Text PDFFront Neurol
August 2025
Department of Rehabilitation Medicine, The First Affiliated Hospital, Fujian Medical University; National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Introduction: Chorea-acanthocytosis (ChAc) is the most common subtype of neuroacanthocytosis (NA) caused by mutations in VPS13A (vacuole protein sorting-associated protein 13A). ChAc is characterized by the presence of spherocytes and neurological symptoms. This article reports two families with ChAc and summarizes some suggestive characteristics, providing an effective basis for clinicians to screen ChAc in the early stage and effectively reduce the misdiagnosis and missed diagnosis of this disease.
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