Structural basis of human VANGL-PRICKLE interaction.

Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-like (VANGL)-PRICKLE (PK) pair is one of these two key regulators; however, their structural information and detailed functions have been unclear.

Securin acetylation prevents precocious separase activation and premature sister chromatid separation.

Lysine acetylation of non-histone proteins plays crucial roles in many cellular processes. In this study, we examine the role of lysine acetylation during sister chromatid separation in mitosis. We investigate the acetylation of securin at K21 by cell-cycle-dependent acetylome analysis and uncover its role in separase-triggered chromosome segregation during mitosis.

SCG10 is required for peripheral axon maintenance and regeneration in mice.

Proper microtubule dynamics are critical for neuronal morphogenesis and functions, and their dysregulation results in neurological disorders and regeneration failure. Superior cervical ganglion-10 (SCG10, also known as stathmin-2 or STMN2) is a well-known regulator of microtubule dynamics in neurons, but its functions in the peripheral nervous system remain largely unknown. Here, we show that Scg10 knockout mice exhibit severely progressive motor and sensory dysfunctions with significant sciatic nerve myelination deficits and neuromuscular degeneration.

CCDC115 inhibits autophagy-mediated degradation of YAP to promote cell proliferation.

Autophagy and Hippo signalling pathways both play important roles in cell homeostasis and are often involved in tumourigenesis. However, the crosstalk between these two signal pathways in response to stress conditions, such as nutrient deficiency, is incompletely understood. Here, we show that vesicular localised coiled-coil domain containing 115 (CCDC115) inhibits autophagy as well as Hippo signalling pathway under starvation.

Ligand-free mitochondria-localized mutant AR-induced cytotoxicity in spinal bulbar muscular atrophy.

Spinal bulbar muscular atrophy (SBMA), the first identified CAG-repeat expansion disorder, is an X-linked neuromuscular disorder involving CAG-repeat-expansion mutations in the androgen receptor (AR) gene. We utilized CRISPR-Cas9 gene editing to engineer novel isogenic human induced pluripotent stem cell (hiPSC) models, consisting of isogenic AR knockout, control and disease lines expressing mutant AR with distinct repeat lengths, as well as control and disease lines expressing FLAG-tagged wild-type and mutant AR, respectively. Adapting a small-molecule cocktail-directed approach, we differentiate the isogenic hiPSC models into motor neuron-like cells with a highly enriched population to uncover cell-type-specific mechanisms underlying SBMA and to distinguish gain- from loss-of-function properties of mutant AR in disease motor neurons.

Transverse endoplasmic reticulum expansion in hereditary spastic paraplegia corticospinal axons.

Hereditary spastic paraplegias (HSPs) comprise a large group of inherited neurologic disorders affecting the longest corticospinal axons (SPG1-86 plus others), with shared manifestations of lower extremity spasticity and gait impairment. Common autosomal dominant HSPs are caused by mutations in genes encoding the microtubule-severing ATPase spastin (SPAST; SPG4), the membrane-bound GTPase atlastin-1 (ATL1; SPG3A) and the reticulon-like, microtubule-binding protein REEP1 (REEP1; SPG31). These proteins bind one another and function in shaping the tubular endoplasmic reticulum (ER) network.

ER proteins decipher the tubulin code to regulate organelle distribution.

Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions. However, how cells interpret these post-translational microtubule modification codes to selectively regulate organelle positioning remains largely unknown. The endoplasmic reticulum (ER) is an interconnected network of diverse morphologies that extends promiscuously throughout the cytoplasm, forming abundant contacts with other organelles.

Self-Propelled and Near-Infrared-Phototaxic Photosynthetic Bacteria as Photothermal Agents for Hypoxia-Targeted Cancer Therapy.

Hypoxia can increase the resistance of tumor cells to radiotherapy and chemotherapy. However, the dense extracellular matrix, high interstitial fluid pressure, and irregular blood supply often serve as physical barriers to inhibit penetration of drugs or nanodrugs across tumor blood microvessels into hypoxic regions. Therefore, it is of great significance and highly desirable to improve the efficiency of hypoxia-targeted therapy.

Calumenin-1 Interacts with Climp63 to Cooperatively Determine the Luminal Width and Distribution of Endoplasmic Reticulum Sheets.

The ER is composed of distinct structures like tubules, matrices, and sheets, all of which are important for its various functions. However, how these distinct ER structures, especially the perinuclear ER sheets, are formed remains unclear. We report here that the ER membrane protein Climp63 and the ER luminal protein calumenin-1 (Calu1) collaboratively maintain ER sheet morphology.

DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B.

Autophagosome and lysosome fusion is an important macroautophagy/autophagy process for cargo degradation, and SNARE proteins, including STX17, SNAP29, VAMP7 and VAMP8, are key players in this process. However, the manner in which this process is precisely regulated is poorly understood. Here, we show that VAMP7B, a SNARE domain-disrupted isoform of R-SNARE protein VAMP7, competes with SNARE domain functional isoform VAMP7A to bind to STX17 and inhibits autophagosome-lysosome fusion.

ATL3 Is a Tubular ER-Phagy Receptor for GABARAP-Mediated Selective Autophagy.

The endoplasmic reticulum (ER) consists of the nuclear envelope and both peripheral ER sheets and a peripheral tubular network [1, 2]. In response to physiological or pathological conditions, receptor-mediated selective ER-phagy, engulfing specific ER subdomains or components, is essential for ER turnover and homeostasis [3-6]. Four mammalian receptors for ER-phagy have been reported: FAM134B [7], reticulon 3 (RTN3) [8], SEC62 [9], and CCPG1 [10].

DNA damage triggers tubular endoplasmic reticulum extension to promote apoptosis by facilitating ER-mitochondria signaling.

The endoplasmic reticulum (ER) is composed of the nuclear envelope, perinuclear sheets and a peripheral tubular network. The peripheral ER and mitochondria form tight contacts at specific subdomains, which coordinate the functions of the two organelles and are required for multiple cellular processes such as Ca transfer and apoptosis. However, it is largely unknown how ER morphology and ER-mitochondria signaling are dynamically regulated under different physiological or pathological conditions such as DNA damage.

Biomimetic O-Evolving metal-organic framework nanoplatform for highly efficient photodynamic therapy against hypoxic tumor.

Improving the supply of O and the circulation lifetime of photosensitizers for photodynamic therapy (PDT) in vivo would be a promising approach to eliminate hypoxic tumors. Herein, by taking advantage of the significant gas-adsorption capability of metal-organic frameworks (MOFs), a biomimetic O-evolving photodynamic therapy (PDT) nanoplatform with long circulating properties was fabricated. Zirconium (IV)-based MOF (UiO-66) was used as a vehicle for O storing, then conjugated with indocyanine green (ICG) by coordination reaction, and further coated with red blood cell (RBC) membranes.

Characterization of actin and tubulin promoters from two sap-sucking pests, Nilaparvata lugens (Stål) and Nephotettix cincticeps (Uhler).

The brown planthopper, Nilaparvata lugens (N. lugens, Hemiptera: Delphacidae), and the green rice leafhopper, Nephotettix cincticeps (N. cincticeps, Hemiptera: Cicadellidae), two sap-sucking feeders, have caused many destructive agricultural disasters in East Asia, as they can bring diseases like 'hopper burn' and transmit plant viruses.

Calumenin and fibulin-1 on tumor metastasis: Implications for pharmacology.

Tumor metastasis is a key cause of cancer mortality, and inhibiting migration of cancer cells is one of the major directions of anti-metastatic drug development. Calumenin and fibulin-1 are two extracellular proteins that synergistically inhibit cell migration and tumor metastasis, and could potentially be served as targets for pharmacological research of anti-metastatic drugs. This review briefly introduces the multi-function of these two proteins, and discusses the mechanism of how they regulate cell migration and tumor metastasis.

Trip6 promotes dendritic morphogenesis through dephosphorylated GRIP1-dependent myosin VI and F-actin organization.

Thyroid receptor-interacting protein 6 (Trip6), a multifunctional protein belonging to the zyxin family of LIM proteins, is involved in various physiological and pathological processes, including cell migration and tumorigenesis. However, the role of Trip6 in neurons remains unknown. Here, we show that Trip6 is expressed in mouse hippocampal neurons and promotes dendritic morphogenesis.

BmCREC is an endoplasmic reticulum (ER) resident protein and required for ER/Golgi morphology.

Silkworm posterior silkgland is a model for studying intracellular trafficking. Here, using this model, we identify several potential cargo proteins of BmKinesin-1 and focus on one candidate, BmCREC. BmCREC (also known as Bombyx mori DNA supercoiling factor, BmSCF) was previously proposed to supercoil DNA in the nucleus.

The intracellular transport and secretion of calumenin-1/2 in living cells.

Calumenin isoforms 1 and 2 (calu-1/2), encoded by the CALU gene, belong to the CREC protein family. Calu-1/2 proteins are secreted into the extracellular space, but the secretory process and regulatory mechanism are largely unknown. Here, using a time-lapse imaging system, we visualized the intracellular transport and secretory process of calu-1/2-EGFP after their translocation into the ER lumen.

Silkworm coatomers and their role in tube expansion of posterior silkgland.

Background: Coat protein complex I (COPI) vesicles, coated by seven coatomer subunits, are mainly responsible for Golgi-to-ER transport. Silkworm posterior silkgland (PSG), a highly differentiated secretory tissue, secretes fibroin for silk production, but many physiological processes in the PSG cells await further investigation.

Methodology/principal Findings: Here, to investigate the role of silkworm COPI, we cloned six silkworm COPI subunits (α, β, β', δ, ε, and ζ-COP), determined their peak expression in day 2 in fifth-instar PSG, and visualized the localization of COPI, as a coat complex, with cis-Golgi.