Decision letter: Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling

Cilia project from the surface of most vertebrate cells and are important for several physiological and developmental processes. Ciliary defects are linked to a variety of human diseases, named ciliopathies, underscoring the importance of understanding signaling pathways involved in cilia formation and maintenance. In this paper, we identified Rer1p as the first endoplasmic reticulum/cis-Golgi–localized membrane protein involved in ciliogenesis. Rer1p, a protein quality control receptor, was highly expressed in zebrafish ciliated organs and regulated ciliary structure and function. Both in zebrafish and mammalian cells, loss of Rer1p resulted in the shortening of cilium and impairment of its motile or sensory function, which was reflected by hearing, vision, and left–right asymmetry defects as well as decreased Hedgehog signaling. We further demonstrate that Rer1p depletion reduced ciliary length and function by increasing γ-secretase complex assembly and activity and, consequently, enhancing Notch signaling as well as reducing Foxj1a expression.

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LRIG1 Extracellular Domain: Structure and Function Analysis

Journal of Molecular Biology ◽

10.1016/j.jmb.2015.03.001 ◽

2015 ◽

Vol 427 (10) ◽

pp. 1934-1948 ◽

Cited By ~ 7

Author(s):

Yibin Xu ◽

Priscilla Soo ◽

Francesca Walker ◽

Hui Hua Zhang ◽

Nicholas Redpath ◽

...

Keyword(s):

Domain Structure ◽

Function Analysis ◽

Extracellular Domain ◽

Structure And Function ◽

And Function

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Intein Inhibitors as Novel Antimicrobials: Protein Splicing in Human Pathogens, Screening Methods, and Off-Target Considerations

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.752824 ◽

2021 ◽

Vol 8 ◽

Author(s):

Diana A. Wall ◽

Seanan P. Tarrant ◽

Chunyu Wang ◽

Kenneth V. Mills ◽

Christopher W. Lennon

Keyword(s):

Hedgehog Signaling ◽

Structure And Function ◽

Screening Methods ◽

Protein Splicing ◽

Proof Of Concept ◽

Human Pathogens ◽

Microbial World ◽

Essential Proteins ◽

And Function ◽

Translational Process

Protein splicing is a post-translational process by which an intervening polypeptide, or intein, catalyzes its own removal from the flanking polypeptides, or exteins, concomitant with extein ligation. Although inteins are highly abundant in the microbial world, including within several human pathogens, they are absent in the genomes of metazoans. As protein splicing is required to permit function of essential proteins within pathogens, inteins represent attractive antimicrobial targets. Here we review key proteins interrupted by inteins in pathogenic mycobacteria and fungi, exciting discoveries that provide proof of concept that intein activity can be inhibited and that this inhibition has an effect on the host organism’s fitness, and bioanalytical methods that have been used to screen for intein activity. We also consider potential off-target inhibition of hedgehog signaling, given the similarity in structure and function of inteins and hedgehog autoprocessing domains.

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Astrocyte regulation of neuron structure and function mediated by Sonic hedgehog signaling

10.17918/00000564 ◽

2021 ◽

Author(s):

Steven A. Hill

Keyword(s):

Sonic Hedgehog ◽

Hedgehog Signaling ◽

Structure And Function ◽

Sonic Hedgehog Signaling ◽

And Function

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Insights into the structure and function of the extracellular domain of alpha‐neurexin by single particle EM and surface plasmon resonance

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.823.18 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Meghan Thorne Miller ◽

Davide Comoletti ◽

Jennifer Wilson ◽

Teru Nakagawa ◽

Palmer Taylor

Keyword(s):

Surface Plasmon Resonance ◽

Surface Plasmon ◽

Plasmon Resonance ◽

Single Particle ◽

Extracellular Domain ◽

Structure And Function ◽

And Function

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Structure and Function of Integrin Extracellular Domain

Japanese Journal of Thrombosis and Hemostasis ◽

10.2491/jjsth.9.176 ◽

1998 ◽

Vol 9 (3) ◽

pp. 176-185

Author(s):

Kenji YOKOYAMA ◽

Yoshikazu TAKADA

Keyword(s):

Extracellular Domain ◽

Structure And Function ◽

And Function

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Structure and function of neural networks in the retina

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100102213 ◽

1988 ◽

Vol 46 ◽

pp. 26-27

Author(s):

Peter Sterling

Keyword(s):

Ganglion Cells ◽

Three Dimensional ◽

Structure And Function ◽

Synaptic Connections ◽

Visual Axis ◽

One Dimensional ◽

Cat Retina ◽

Ultrathin Sections ◽

And Function ◽

Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

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Osseointegration interface of calcified bone and endosseous implants

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100130110 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1096-1097

Author(s):

K.E. Krizan ◽

J.E. Laffoon ◽

M.J. Buckley

Keyword(s):

Structure And Function ◽

Titanium Implants ◽

En Bloc ◽

Endosseous Implants ◽

Ultrastructural Studies ◽

The Past ◽

Cacodylate Buffer ◽

One Year ◽

And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

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Use of human autoantibodies and immunoelectron microscopy to study structure and function of the nucleolus and nuclear bodies

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122939 ◽

1992 ◽

Vol 50 (1) ◽

pp. 506-507

Author(s):

Robert L. Ochs

Keyword(s):

Electron Microscopy ◽

Structure And Function ◽

Nuclear Bodies ◽

Nuclear Interior ◽

Coiled Bodies ◽

Interchromatin Granules ◽

And Function ◽

Conventional Electron Microscopy ◽

Perichromatin Granules ◽

Perichromatin Fibrils

By conventional electron microscopy, the formed elements of the nuclear interior include the nucleolus, chromatin, interchromatin granules, perichromatin granules, perichromatin fibrils, and various types of nuclear bodies (Figs. 1a-c). Of these structures, all have been reasonably well characterized structurally and functionally except for nuclear bodies. The most common types of nuclear bodies are simple nuclear bodies and coiled bodies (Figs. 1a,c). Since nuclear bodies are small in size (0.2-1.0 μm in diameter) and infrequent in number, they are often overlooked or simply not observed in any random thin section. The rat liver hepatocyte in Fig. 1b is a case in point. Historically, nuclear bodies are more prominent in hyperactive cells, they often occur in proximity to nucleoli (Fig. 1c), and sometimes they are observed to “bud off” from the nucleolar surface.

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