Search results for "Connectin"
showing 10 items of 27 documents
Centrins, gatekeepers for the light-dependent translocation of transducin through the photoreceptor cell connecting cilium
2006
Centrins are members of a highly conserved subgroup of the EF-hand superfamily of Ca(2+)-binding proteins commonly associated with centrosome-related structures. In the retina, centrins are also prominent components of the photoreceptor cell ciliary apparatus. Centrin isoforms are differentially localized at the basal body and in the lumen of the connecting cilium. All molecular exchanges between the inner and outer segments occur through this narrow connecting cilium. Ca(2+)-activated centrin isoforms bind to the visual heterotrimeric G-protein transducin via an interaction with the betagamma-subunit. Ca(2+)-dependent assemblies of centrin/G-protein complexes may regulate the transducin mo…
Association of Whirlin with Cav1.3 (α1D) Channels in Photoreceptors, Defining a Novel Member of the Usher Protein Network
2010
Contains fulltext : 88383.pdf (Publisher’s version ) (Closed access) PURPOSE: Usher syndrome is the most common form of hereditary deaf-blindness. It is both clinically and genetically heterogeneous. The USH2D protein whirlin interacts via its PDZ domains with other Usher-associated proteins containing a C-terminal type I PDZ-binding motif. These proteins co-localize with whirlin at the region of the connecting cilium and at the synapse of photoreceptor cells. This study was undertaken to identify novel, Usher syndrome-associated, interacting partners of whirlin and thereby obtain more insights into the function of whirlin. METHODS: The database of ciliary proteins was searched for proteins…
Matrix metalloproteinase-12 cleaved fragment of titin as a predictor of functional capacity in patients with heart failure and preserved ejection fra…
2020
Serum levels of matrix metalloproteinase-12 cleaved fragment of titin (TIM), a novel circulatory biomarker specific for cardiac titin degradation, has emerged as a potential biomarker in cardiovascular diseases. In this work, we aimed to evaluate the association between TIM and maximal functional capacity assessed by the percentage of predicted peak exercise oxygen uptake (pp-peakVO2) in patients with heart failure and preserved ejection fraction (HFpEF). Design. In this post-hoc study, we included 46 stable symptomatic (New York Heart Association II-III) HFpEF patients enrolled in the TRAINING-HF study (NCT02638961). pp-peak-VO2 was calculated from baseline values. Baseline circulating lev…
Evidence for Myosin VIIa-Driven Transport of Rhodopsin in the Plasma Membrane of the Photoreceptor-Connecting Cilium
2007
Defects in the gene encoding for the unconventional myosin VIIa leads to human Usher syndrome 1B, the most common form of hereditary combined blindness and deafness. To determine cellular function of myosin VIIa, we have investigated the subcellular localization of myosin VIIa in spacial relation relationship to potentially interacting proteins in mammalian photoreceptor cells. Western blot analysis of the axonemal fraction of photoreceptor cells by Western blot show that myosin VIIa and actin, as well as opsin, were present in the ciliary portion of the photoreceptors. Improved immunoelectron microscopy revealed that in mammalian photoreceptor cells, myosin VIIa was localized at the membra…
C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor prima…
2015
Background/aim We have noted a phenotype of early-onset retinal dystrophy with macular staphyloma but without high myopia. The aim of this study is to report the underlying genetic mutations and the subcellular localisation of the gene product in the retina. Methods Retrospective case series (2012–2015); immunohistochemical analyses of mammalian retina for in situ protein localisation. Results All three probands were first noted to have decreased vision at 3–6 years old which worsened over time. At ages 39, 37 and 12 years old, all had similar retinal findings: dystrophic changes (retinal pigment epithelium mottling, vessel narrowing), macular staphyloma (despite only mild myopia or high hy…
Identification of Novel Molecular Components of the Photoreceptor Connecting Cilium by Immunoscreens
2002
Abstract The connecting cilium of photoreceptor cells is the only intracellular link between the morphologically, functionally and biochemically different compartments of the inner and outer segments. The non-motile modified cilium plays an important role in the organization and the function of photoreceptor cells, namely in delivery and turnover of enzymes and substrates of the visual transduction cascade, and the photosensitive membranes of the outer segment. The protein components of the cilium participate in the intracellular transport through the cilium, in the outer segment disk morphogenesis and in the maintenance of discrete membrane domains. In order to identify yet unknown cytoske…
Insights into functional aspects of centrins from the structure of N-terminally extended mouse centrin 1
2006
AbstractCentrins are members of the family of Ca2+-binding EF-hand proteins. In photoreceptor cells, centrin isoform 1 is specifically localized in the non-motile cilium. This connecting cilium links the light-sensitive outer segment with the biosynthetic active inner segment of the photoreceptor cell. All intracellular exchanges between these compartments have to occur through this cilium. Three-dimensional structures of centrins from diverse organisms are known, showing that the EF-hand motifs of the N-terminal domains adopt closed conformations, while the C-terminal EF-hand motifs have open conformations. The crystal structure of an N-terminally extended mouse centrin 1 (MmCen1-L) resemb…
Recurrence and genericity
2003
We prove a C^1-connecting lemma for pseudo-orbits of diffeomorphisms on compact manifolds. We explore some consequences for C^1-generic diffeomorphisms. For instance, C^1-generic conservative diffeomorphisms are transitive. Nous montrons un lemme de connexion C^1 pour les pseudo-orbites des diffeomorphismes des varietes compactes. Nous explorons alors les consequences pour les diffeomorphismes C^1-generiques. Par exemple, les diffeomorphismes conservatifs C^1-generiques sont transitifs.
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…
Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells
2000
The transport of the photopigment rhodopsin from the inner segment to the photosensitive outer segment of vertebrate photoreceptor cells has been one of the main remaining mysteries in photoreceptor cell biology. Because of the lack of any direct evidence for the pathway through the photoreceptor cilium, alternative extracellular pathways have been proposed. Our primary aim in the present study was to resolve rhodopsin trafficking from the inner to the outer segment. We demonstrate, predominantly by high-sensitive immunoelectron microscopy, that rhodopsin is also densely packed in the membrane of the photoreceptor connecting cilium. Present prominent labeling of rhodopsin in the ciliary mem…