Search results for "Nerve Tissue Protein"
showing 10 items of 345 documents
SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes
2021
Abstract Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome—the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal sub-complexes such as SF3B1 and the large splicing cofact…
Integrative proteomics: functional and molecular characterization of a particular glutamate-related neuregulin isoform.
2005
Glutamate is the major excitatory neurotransmitter in the mammalian brain and is related to memory by calcium-conducting receptors. Neuregulins have emerged as long-term modulating molecules of synaptic signaling by glutamate receptors, playing a role in some cognition/memory-related disorders and moreover being part of transient functional microdomains, called lipid rafts. Here we characterize one specific isoform of neuregulin as a central biomarker for glutamate-related signaling, integrating results from in vitro and in vivo models by a differential functional and proteomic approach.
Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon?
2007
Indirect evidence for disturbed structural connectivity of subcortical fiber tracts in schizophrenia has been obtained from functional neuroimaging and electrophysiologic studies. During the past few years, new structural imaging methods have become available. Diffusion tensor imaging and magnetization transfer imaging (MTI) have been used to investigate directly whether fiber tract abnormalities are indeed present in schizophrenia. To date, findings are inconsistent that may express problems related to methodological issues and sample size. Also, pathological processes detectable with these new techniques are not yet well understood. Nevertheless, with growing evidence of disturbed structu…
A New Type of Cytokine Receptor Antagonist Directly Targeting gp130
1998
The interleukin-6-type family of cytokines bind to receptor complexes that share gp130 as a common signal-transducing subunit. So far, receptor antagonists for interleukin-6-type cytokines have been constructed that still bind to the specific ligand binding subunit of the receptor complex, but have lost the ability to stimulate gp130. Such receptor antagonists compete for a specific receptor of a member of the cytokine family. Interleukin-6 only binds to gp130 when complexed with the interleukin-6 receptor that exists as a membrane bound and soluble molecule. Here we have constructed fusion proteins that consist of the soluble form of the human interleukin-6 receptor covalently linked to in…
Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system.
2014
The proper functioning of the dopaminergic system requires the coordinated formation of projections extending from dopaminergic neurons in the substantia nigra (SN), ventral tegmental area (VTA) and retrorubral field to a wide array of forebrain targets including the striatum, nucleus accumbens and prefrontal cortex. The mechanisms controlling the assembly of these distinct dopaminergic cell clusters are not well understood. Here, we have investigated in detail the migratory behavior of dopaminergic neurons giving rise to either the SN or the medial VTA using genetic inducible fate mapping, ultramicroscopy, time-lapse imaging, slice culture and analysis of mouse mutants. We demonstrate that…
Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety,…
2011
Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (M…
Identification of a β-Dystroglycan Immunoreactive Subcompartment in Photoreceptor Terminals
2005
PURPOSE Mutations in the dystrophin-associated glycoprotein complex (DGC) cause various forms of muscular dystrophy. These diseases are characterized by progressive loss of skeletal muscle tissue and by dysfunctions in the central nervous system (CNS). The CNS deficits include an altered electroretinogram, caused by an impaired synaptic transmission between photoreceptors and their postsynaptic target cells in the outer plexiform layer (OPL). The DGC is concentrated in the OPL but its exact distribution is controversial. Therefore, the precise distribution of beta-dystroglycan, the central component of the DGC, within the OPL of the mature chick retina, was determined. METHODS Double immuno…
Connecting temporal identity to mitosis: the regulation of Hunchback in Drosophila neuroblast lineages.
2006
Both in vertebrates and invertebrates, neural stem cells generate different cell types at different times during development. It has been suggested that this process depends on temporal identity transitions of neural progenitors, but the underlying mechanism has not been resolved, yet. Recently, Drosophila neuroblasts (NBs) have been shown to be an excellent model system to investigate this subject. Here, changes in temporal identity are regulated by sequential and transient expression of transcription factors in the NB, such as Hunchback (Hb) and Kruppel (Kr). The temporal expression profile is maintained in the progeny. Hb is expressed first and thus defines the earliest identity in a giv…
A key role for cyclic nucleotide gated (CNG) channels in cGMP-related retinitis pigmentosa.
2011
The rd1 natural mutant is one of the first and probably the most commonly studied mouse model for retinitis pigmentosa (RP), a severe and frequently blinding human retinal degeneration. In several decades of research, the link between the increase in photoreceptor cGMP levels and the extremely rapid cell death gave rise to a number of hypotheses. Here, we provide clear evidence that the presence of cyclic nucleotide gated (CNG) channels in the outer segment membrane is the key to rod photoreceptor loss. In Cngb1(-/-) x rd1 double mutants devoid of regular CNG channels, cGMP levels are still pathologically high, but rod photoreceptor viability and outer segment morphology are greatly improve…
SANS (USH1G) expression in developing and mature mammalian retina
2008
AbstractThe human Usher syndrome (USH) is the most common form of combined deaf-blindness. Usher type I (USH1), the most severe form, is characterized by profound congenital deafness, constant vestibular dysfunction and prepubertal-onset of retinitis pigmentosa. Five corresponding genes of the six USH1 genes have been cloned so far. The USH1G gene encodes the SANS (scaffold protein containing ankyrin repeats and SAM domain) protein which consists of protein motifs known to mediate protein–protein interactions. Recent studies indicated SANS function as a scaffold protein in the protein interactome related to USH.Here, we generated specific antibodies for SANS protein expression analyses. Our…