A5034860044- Nuclear Structure and Function
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Myasthenia Gravis and Thymoma
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- Trace Elements in Health
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Neurogenesis and neuroplasticity mechanisms
- RNA modifications and cancer
- Axon Guidance and Neuronal Signaling
- Signaling Pathways in Disease
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Nerve injury and regeneration
- DNA Repair Mechanisms
University of Basel
2010-2024
University of Dundee
2003-2004
Nucleocytoplasmic transport is sustained by karyopherins (Kaps) and a Ran guanosine triphosphate (RanGTP) gradient that imports nuclear localization signal (NLS)–specific cargoes (NLS-cargoes) into the nucleus. However, how pore complex (NPC) barrier selectivity, Kap traffic, NLS-cargo release are systematically linked simultaneously regulated remains incoherent. In this study, we show Kapα facilitates Kapβ1 turnover occupancy at NPC in RanGTP-dependent manner directly coupled to function....
Nuclear pore complexes (NPCs) discriminate nonspecific macromolecules from importin and exportin receptors, collectively termed “karyopherins” (Kaps), that mediate nucleocytoplasmic transport. This selective barrier function is attributed to the behavior of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups) guard NPC channel. However, NPCs in vivo are typically enriched with different Kaps, how they impact remains unknown. Here, we show two major importinβ1/karyopherinβ1...
The Polycomb Repressive Complex 2 (PRC2) plays important roles in the epigenetic regulation of cellular development and differentiation through H3K27me3-dependent transcriptional repression. Aberrant PRC2 activity has been associated with cancer neurodevelopmental disorders, particularly respect to malfunction sits catalytic subunit EZH2. Here, we investigated role EZH2-mediated H3K27me3 apposition neuronal differentiation. We made use a transgenic mouse model harboring
Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization exportins cytoplasm is linked disease. Hence, it important understand how their containment within regulated. Here, we have studied nuclear efflux exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα importinα), cargo adaptor for karyopherinβ1 (Kapβ1 importinβ1), a Ran guanosine triphosphate (RanGTP)-mediated manner. We show N-terminus CAS...
Ran is a small GTPase whose nucleotide-bound forms cycle through nuclear pore complexes (NPCs) to direct nucleocytoplasmic transport (NCT). Generally, guanosine triphosphate (RanGTP) binds cargo-carrying karyopherin receptors (Kaps) in the nucleus and releases them into cytoplasm following hydrolysis diphosphate (RanGDP). This generates remarkably steep gradient across envelope that sustains compartment-specific cargo delivery accumulation. However, because NPCs are permeable molecules of...
Abstract Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group inherited disorders characterised by impaired neuromuscular transmission. Most CMS originate from defects in muscle nicotinic acetylcholine receptor, but underlying molecular pathogenesis is only poorly understood. Here we show that RNAi-mediated silencing FADS-related proteins rapsyn and NUP88 foetal fibroblasts alters organisation actin cytoskeleton. We...
Abstract Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group inherited disorders characterised by impaired neuromuscular transmission. Most CMS originate from defects in muscle nicotinic acetylcholine receptor, but underlying molecular pathogenesis is only poorly understood. Here we show that RNAi-mediated silencing FADS-related proteins rapsyn and NUP88 foetal fibroblasts alters organisation actin cytoskeleton. We...