12 research outputs found
Transient accumulation and bidirectional movement of KIF13B in primary cilia.
Primary cilia are microtubule-based sensory organelles
whose assembly and function rely on the conserved bidirectional
intraflagellar transport (IFT) system, which is powered by anterograde
kinesin-2 and retrograde cytoplasmic dynein-2 motors. Nematodes
additionally employ a cell-type-specific kinesin-3 motor, KLP-6,
which moves within cilia independently of IFT and regulates ciliary
content and function. Here, we provide evidence that a KLP-6
homolog, KIF13B, undergoes bursts of bidirectional movement
within primary cilia of cultured immortalized human retinal
pigment epithelial (hTERT-RPE1) cells. Anterograde and retrograde
intraciliary velocities of KIF13B were similar to those of IFT
(as assayed using IFT172–eGFP), but intraciliary movement of
KIF13B required its own motor domain and appeared to be cell-type
specific. Our work provides the first demonstration of motor-driven,
intraciliary movement by a vertebrate kinesin other than kinesin-2
motors.post-print449 K
TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome
The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel–Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome1 (JBTS). However, the molecular composition and mechanisms underpinning TZ organization and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (coexpression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral–facial–digital syndrome and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237). Finally, MKS module membrane proteins are immobile and super-resolution microscopy in worms and mammalian cells reveals periodic localizations within the TZ. This work expands the MKS module of ciliopathy-causing TZ proteins associated with diffusion barrier formation and provides insight into TZ subdomain architecture
Cutting Edge: Expression of IL-1 Receptor-Associated Kinase-4 (IRAK-4) Proteins with Mutations Identified in a Patient with Recurrent Bacterial Infections Alters Normal IRAK-4 Interaction with Components of the IL-1 Receptor Complex
Rab35 controls cilium length, function and membrane composition
International audienceRab and Arl guanine nucleotide-binding (G) proteins regulate trafficking pathways essential for the formation, function and composition of primary cilia, which are sensory devices associated with Sonic hedgehog (Shh) signalling and ciliopathies. Here, using mammalian cells and zebrafish, we uncover ciliary functions for Rab35, a multitasking G protein with endocytic recycling, actin remodelling and cytokinesis roles. Rab35 loss via siRNAs, morpholinos or knockout reduces cilium length in mammalian cells and the zebrafish left-right organiser (Kupffer's vesicle) and causes motile cilia-associated left-right asymmetry defects. Consistent with these observations, GFP-Rab35 localises to cilia, as do GEF (DENND1B) and GAP (TBC1D10A) Rab35 regulators, which also regulate ciliary length and Rab35 ciliary localisation. Mammalian Rab35 also controls the ciliary membrane levels of Shh signalling regulators, promoting ciliary targeting of Smoothened, limiting ciliary accumulation of Arl13b and the inositol polyphosphate 5-phosphatase (INPP5E). Rab35 additionally regulates ciliary PI(4,5)P2 levels and interacts with Arl13b. Together, our findings demonstrate roles for Rab35 in regulating cilium length, function and membrane composition and implicate Rab35 in pathways controlling the ciliary levels of Shh signal regulators
The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone
Tecnologie digitali per la valorizzazione del patrimonio culturale. La rappresentazione di beni non accessibili
Il contributo rientra nel filone delle sperimentazioni di comunicazione multimediale e di ricostruzione virtuale di architetture e frammenti urbani.
Il lavoro presenta i risultati di alcune applicazioni digitali che adoperano il linguaggio multimediale per consentire la fruizione virtuale di siti per diverse ragioni non accessibili, per raccontare un percorso reale o concettuale.
I casi studio analizzati si configurano quali possibili prodotti strategici di divulgazione e comunicazione per la conoscenza e la comprensione del patrimonio culturale e per la veicolazione di contenuti scientifici.The contribution is part of the study and experimentation of multimedia communication, virtual analysis and reconstruction of architectures and urban fragments.
This paper shows the results of some digital applications that use multimedia language for virtual fruition and enhancement of some sites, which for several reasons, are not accessible, to tell a real or conceptual path.
The cases analyzed are considered as possible strategic products of dissemination and communication for the knowledge and understanding of cultural heritage and for the transmission of scientific content
Additional file 4: of KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome
IFT analysis in C. elegans K04F10.2( tm1830 ) mutants. a Intraflagellar transport rates in wild-type and K04F10.2(tm1830) mutant worms. Shown are the anterograde and retrograde velocities (μm.s-1/standard deviation (SD)) of GFP-tagged IFT proteins along amphid and phasmid channel cilia (combined; top rows), or phasmid cilia only (bottom rows). t-test pairwise comparison with wild-type controls, n number of particles, N measured number of amphids and phasmids. OSM-3 is the worm orthologue of KIF17; CHE-11 is the worm orthologue of IFT140; OSM-6 is the worm orthologue of IFT52. b Representative fluorescence images of phasmid cilia showing normal IFT protein localisations and distributions in tm1830 mutants. ds distal segment, ms middle segment, bb basal body region, den dendrite. All images are similarly scaled and orientated (arrow denotes basal body). Scale bar, 3 μm. c Representative kymographs (time (t) over distance (d) plots) used to generate IFT rate measurements. For each kymograph, the horizontal axis (distance) is 5 μm and the vertical axis (time) is 25 seconds. d Distribution plots of IFT protein velocities. (JPG 1951 kb