The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture.

Cilia are essential organelles and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis in animals models but remains poorly defined. Notably, all but one subunit of the CPLANE complex have been implicated in human ciliopathy.

Astrocyte-Specific Inhibition of the Primary Cilium Suppresses C3 Expression in Reactive Astrocyte.

C3-positive reactive astrocytes play a neurotoxic role in various neurodegenerative diseases. However, the mechanisms controlling C3-positive reactive astrocyte induction are largely unknown. We found that the length of the primary cilium, a cellular organelle that receives extracellular signals was increased in C3-positive reactive astrocytes, and the loss or shortening of primary cilium decreased the count of C3-positive reactive astrocytes.

Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration.

Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction.

Corrigendum: Dendritic cell proliferation by primary cilium in atopic dermatitis.

[This corrects the article DOI: 10.3389/fmolb.2023.

Dephosphorylation of neural wiring protein shootin1 by PP1 phosphatase regulates netrin-1-induced axon guidance.

Axon pathfinding is an essential step in neuronal network formation. Shootin1a is a clutch-linker molecule that is mechanically involved in axon outgrowth and guidance. It was previously shown that concentration gradients of axon guidance molecule netrin-1 in the extracellular environment elicit asymmetrically localized Pak1 kinase-mediated phosphorylation of shootin1a within axonal growth cones, which is higher on the netrin-1 source side.

Hedgehog Signal and Genetic Disorders.

The hedgehog (Hh) family comprises sonic hedgehog (Shh), Indian hedgehog (Ihh), and desert hedgehog (Dhh), which are versatile signaling molecules involved in a wide spectrum of biological events including cell differentiation, proliferation, and survival; establishment of the vertebrate body plan; and aging. These molecules play critical roles from embryogenesis to adult stages; therefore, alterations such as abnormal expression or mutations of the genes involved and their downstream factors cause a variety of genetic disorders at different stages. The Hh family involves many signaling mediators and functions through complex mechanisms, and achieving a comprehensive understanding of the entire signaling system is challenging.

Gradient-reading and mechano-effector machinery for netrin-1-induced axon guidance.

Growth cones navigate axonal projection in response to guidance cues. However, it is unclear how they can decide the migratory direction by transducing the local spatial cues into protrusive forces. Here we show that knockout mice of display abnormal projection of the forebrain commissural axons, a phenotype similar to that of the axon guidance molecule netrin-1.

Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis.

Chemical cues presented on the adhesive substrate direct cell migration, a process termed haptotaxis. To migrate, cells must generate traction forces upon the substrate. However, how cells probe substrate-bound cues and generate directional forces for migration remains unclear.

Folate-dependent methylation of septins governs ciliogenesis during neural tube closure.

Periconception maternal folic acid (vitamin B) supplementation can reduce the prevalence of neural tube defects (NTDs), although just how folates benefit the developing embryo and promote closing of the neural tube and other morphologic processes during development remains unknown. Folate contributes to a 1-carbon metabolism, which is essential for purine biosynthesis and methionine recycling and affects methylation of DNA, histones, and nonhistone proteins. Herein, we used animal models and cultured mammalian cells to demonstrate that disruption of the methylation pathway mediated by folate compromises normal neural tube closure (NTC) and ciliogenesis.

The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.

Cilia use microtubule-based intraflagellar transport (IFT) to organize intercellular signaling. Ciliopathies are a spectrum of human diseases resulting from defects in cilia structure or function. The mechanisms regulating the assembly of ciliary multiprotein complexes and the transport of these complexes to the base of cilia remain largely unknown.

Shootin1-cortactin interaction mediates signal-force transduction for axon outgrowth.

Motile cells transduce environmental chemical signals into mechanical forces to achieve properly controlled migration. This signal-force transduction is thought to require regulated mechanical coupling between actin filaments (F-actins), which undergo retrograde flow at the cellular leading edge, and cell adhesions via linker "clutch" molecules. However, the molecular machinery mediating this regulatory coupling remains unclear.

Actin Migration Driven by Directional Assembly and Disassembly of Membrane-Anchored Actin Filaments.

Actin and actin-associated proteins migrate within various cell types. To uncover the mechanism of their migration, we analyzed actin waves, which translocate actin and actin-associated proteins along neuronal axons toward the growth cones. We found that arrays of actin filaments constituting waves undergo directional assembly and disassembly, with their polymerizing ends oriented toward the axonal tip, and that the lateral side of the filaments is mechanically anchored to the adhesive substrate.

Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation.

Soluble guidance cues can direct cellular protrusion and migration by modulating adhesion and cytoskeletal dynamics. Actin filaments (F-actins) polymerize at the leading edge of motile cells and depolymerize proximally [1, 2]; this, together with myosin II activity, induces retrograde flow of F-actins [3-5]. It has been proposed that the traction forces underlying cellular motility may be regulated by the modulation of coupling efficiency between F-actin flow and the extracellular substrate via "clutch" molecules [6-10].

Rab33a mediates anterograde vesicular transport for membrane exocytosis and axon outgrowth.

Axon outgrowth requires plasma membrane expansion, which results from post-Golgi vesicular transport and fusion. However, the molecular mechanisms regulating post-Golgi vesicular trafficking for membrane expansion and axon outgrowth remain unclear. Here, we show that Rab33a expression became upregulated during axon outgrowth of cultured rat hippocampal neurons.

Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration.

Doublecortin (DCX) is a microtubule-associated protein that is specifically expressed in neuronal cells. Genetic mutation of DCX causes lissencephaly disease. Although the abnormal cortical lamination in lissencephaly is thought to be attributable to neuronal cell migration defects, the regulatory mechanisms governing interactions between DCX and cytoskeleton in the migration of neuronal progenitor cells remain obscure.

Structural basis of cargo recognition by the myosin-X MyTH4-FERM domain.

Myosin-X is an important unconventional myosin that is critical for cargo transportation to filopodia tips and is also utilized in spindle assembly by interacting with microtubules. We present a series of structural and biochemical studies of the myosin-X tail domain cassette, consisting of myosin tail homology 4 (MyTH4) and FERM domains in complex with its specific cargo, a netrin receptor DCC (deleted in colorectal cancer). The MyTH4 domain is folded into a helical VHS-like structure and is associated with the FERM domain.

Systems biology of symmetry breaking during neuronal polarity formation.

Polarization, in which a single axon and multiple dendrites are formed, is crucial for neuronal functions, and symmetry breaking is the initial step of this process. Accumulating studies have revealed a number of molecules that act asymmetrically in neurons, and thereby regulate neuronal polarity. Thus, one of the major goals of current research is to understand how asymmetric signals are generated during the symmetry-breaking step.

A diffusion-based neurite length-sensing mechanism involved in neuronal symmetry breaking.

Although there has been significant progress in understanding the molecular signals that change cell morphology, mechanisms that cells use to monitor their size and length to regulate their morphology remain elusive. Previous studies suggest that polarizing cultured hippocampal neurons can sense neurite length, identify the longest neurite, and induce its subsequent outgrowth for axonogenesis. We observed that shootin1, a key regulator of axon outgrowth and neuronal polarization, accumulates in neurite tips in a neurite length-dependent manner; here, the property of cell length is translated into shootin1 signals.

Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth.

Actin polymerizes near the leading edge of nerve growth cones, and actin filaments show retrograde movement in filopodia and lamellipodia. Linkage between actin filament retrograde flow and cell adhesion molecules (CAMs) in growth cones is thought to be one of the mechanisms for axon outgrowth and guidance. However, the molecular basis for this linkage remains elusive.

Gene cloning and biochemical characterization of the BMP-2 of Pinctada fucata.

The bone morphogenetic proteins (BMPs) constitute a subfamily of the transforming growth factor type beta (TGF-beta) supergene family. BMP-2 plays an important role not only in osteoblast differentiation but also in pattern formation during development. To determine the function of BMP-2 in Pinctada fucata development and hard tissue formation, we isolated a BMP-2 genomic DNA clone and the BMP-2 cDNA.

Shootin1: A protein involved in the organization of an asymmetric signal for neuronal polarization.

Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We describe a novel protein, named shootin1, that became up-regulated during polarization of hippocampal neurons and began fluctuating accumulation among multiple neurites.

Acid-labile surfactant improves in-sodium dodecyl sulfate polyacrylamide gel protein digestion for matrix-assisted laser desorption/ionization mass spectrometric peptide mapping.

Mass spectrometry (MS) together with genome database searches serves as a powerful tool for the identification of proteins. In proteome analysis, mixtures of cellular proteins are usually separated by sodium dodecyl sulfate (SDS) polyacrylamide gel-based two-dimensional gel electrophoresis (2-DE) or one-dimensional gel electrophoresis (1-DE), and in-gel digested by a specific protease. In-gel protein digestion is one of the critical steps for sensitive protein identification by these procedures.