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activity-regulated cytoskeletal

Stephen E McGowan, Diann M McCoy
Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ganga Anil Kumar, Kuppuswamy Subramaniam
Pairing of homologous chromosomes is essential for genetic recombination during gametogenesis. In many organisms, chromosome ends are attached to cytoplasmic dynein, and dynein-driven chromosomal movements facilitate the pairing process. Factors that promote / control the cytoskeletal tethering of chromosomes are largely unknown. Here, we show that the conserved RNA-binding protein PUF-8 facilitates the tethering and pairing processes in the C. elegans germline by promoting proteasome activity. We have isolated a hypomorphic allele of pas-1 , which encodes a proteasome core subunit, and find that the homologous chromosomes fail to pair in the puf-8; pas-1 double mutant due to failure of chromosome tethering...
March 14, 2018: Development
Zhimin Du, Ki Hyung Kim, Juil Kim, Yuseok Moon
Adlay is a cereal crop that has long been used as traditional herbal medicine and as a highly nourishing food. However, deoxynivalenol (DON), the most prevalent trichothecene mycotoxin worldwide, frequently spoils grains, including adlay, via fungal infection. On the basis of an assumption that the actions of DON in the gut could be modified by adlay consumption, we simulated the impacts of co-exposure in enterocytes and investigated the effectiveness of treatment with adlay for reducing the risk of DON-induced inflammation and epithelia barrier injury...
2018: Frontiers in Immunology
Aijaz A John, Ravi Prakash, Jyoti Kureel, Divya Singh
We report the role of miR-1187 in regulation of osteoblast functions. Over-expression of miR-1187 inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified BMPR-II and ArhGEF-9 as direct targets of miR-1187. ArhGEF-9 activates Cdc42 which has a major role in actin reorganization. BMP-2 also induces actin polymerization. Role of miR-1187 in actin reorganization was determined by western blotting, immunofluorescence, and in vivo gene silencing studies...
March 9, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Yan Zhang, Nidhi Rohatgi, Deborah J Veis, Joel Schilling, Steven L Teitelbaum, Wei Zou
Osteoclasts are mitochondria-rich cells, but the role of these energy-producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria-inducing co-activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β-deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type...
March 8, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Ravi Kiran Deevi, Arman Javadi, Jane McClements, Jekaterina Vohhodina, Kienan Savage, Maurice Bernard Loughrey, Emma Evergren, Frederick Charles Campbell
Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring...
March 9, 2018: Journal of Pathology
Krzysztof Wrzesinski, Stephen J Fey
The recovery of physiological functionality, which is commonly seen in tissue mimetic three-dimensional (3D) cellular aggregates (organoids, spheroids, acini, etc.), has been observed in cells of many origins (primary tissues, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immortal cell lines). This plurality and plasticity suggest that probably several basic principles promote this recovery process. The aim of this study was to identify these basic principles and describe how they are regulated so that they can be taken in consideration when micro-bioreactors are designed...
March 7, 2018: Bioengineering
M Martinez-Morga, M P Quesada-Rico, C Bueno, S Martinez
AIM: To know the neural processes linked to the activity of brain circuits in order to understand the consequences of their dysfunction and their role in the development of neurodevelopmental diseases, such as autistic spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). DEVELOPMENT: The activity of neuronal circuits is the neurobiological basis of behavior and mental activity (emotions, memory and thoughts). The processes of differentiation of neural cells and the formation of circuits by synaptic contacts between neurons (synaptogenesis) occur in the central nervous system during the late stages of prenatal development and the first months after birth...
March 1, 2018: Revista de Neurologia
Juanjuan Che, Dongsheng Yue, Bin Zhang, Hua Zhang, Yansong Huo, Liuwei Gao, Hongchao Zhen, Yan Yang, Bangwei Cao
Altered expression of claudin-3 (CLDN3), a key cytoskeletal structural protein of the tight junctions in the epithelium, is associated with the development and metastasis of various human cancers. CLDN3 expression has been shown to be significantly associated with the prognosis of lung squamous cell carcinoma (SqCC). This study investigated the role of CLDN3 in inhibiting lung SqCC cell migration and invasion as well as the underlying molecular mechanisms. The CLDN3 levels were assessed between 20 paired lung SqCC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot...
2018: International Journal of Medical Sciences
Jimok Yoon, Jonathan R Terman
To change their size, shape, and connectivity, cells require actin and tubulin proteins to assemble together into long polymers - and numerous extracellular stimuli have now been identified that alter the assembly and organization of these cytoskeletal structures. Yet, there remains a lack of defined signaling pathways from the cell surface to the cytoskeleton for many of these extracellular signals, and so we still know little of how they exert their precise structural effects. These extracellular cues may be soluble or substrate-bound and have historically been classified into two independently acting and antagonistic groups: growth-promoting/attractants (inducing turning toward the source of the factor/positive chemotropism) or growth-preventing/repellents (turning away from the source of the factor/negative chemotropism)...
2018: Communicative & Integrative Biology
Kelei Guo, Xian Lin, Yongtao Li, Wei Qian, Zhong Zou, Huanchun Chen, Hongbo Zhou, Meilin Jin
Non-structural 1 (NS1) protein is a key virulence factor that regulates replication of influenza virus. A recombinant H5N1 virus lacking the eIF4GI-binding domain of NS1 (rNS1-SD30) exhibits significantly lower pathogenicity than H5N1 virus with an intact eIF4GI-binding domain (rNS1-wt). To further investigate this phenomenon, we performed comparative proteomics analyses to profile host proteins in chicken embryo fibroblasts (CEFs) infected with rNS1-wt and rNS1-SD30 viruses. In total, 81 differentially expressed (DE) proteins were identified at 12, 24, and 36 h post-infection...
February 2, 2018: Oncotarget
Andreas Nebenführ, Ram Dixit
Kinesins and myosins are motor proteins that can move actively along microtubules and actin filaments, respectively. Plants have evolved a unique set of motors that function as regulators and organizers of the cytoskeleton and as drivers of long-distance transport of various cellular components. Recent progress has established the full complement of motors encoded in plant genomes and has revealed valuable insights into the cellular functions of many kinesin and myosin isoforms. Interestingly, several of the motors were found to functionally connect the two cytoskeletal systems and thereby to coordinate their activities...
February 28, 2018: Annual Review of Plant Biology
Jing-Yu Xiao, Bing-Rui Xiong, Wen Zhang, Wen-Chang Zhou, Hui Yang, Feng Gao, Hong-Bing Xiang, Anne Manyande, Xue-Bi Tian, Yu-Ke Tian
AIM: Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD. METHODS: Sixteen-month old male C57BL/6J mice were exposed to laparotomy...
February 27, 2018: CNS Neuroscience & Therapeutics
J Scott Lee, Ruth X Wang, Erica E Alexeev, Jordi M Lanis, Kayla D Battista, Louise E Glover, Sean P Colgan
Intestinal epithelial cells form a selectively permeable barrier to protect colon tissues from luminal microbiota and antigens, and to mediate nutrient, fluid, and waste flux in the intestinal tract. Dysregulation of the epithelial cell barrier coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically depleting state of physiological hypoxia. However, studies that systematically examine energy flux and adenylate metabolism during intestinal epithelial barrier development and restoration after disruption are lacking...
February 27, 2018: Journal of Biological Chemistry
Ede Migh, Torsten Götz, István Földi, Szilárd Szikora, Rita Gombos, Zsuzsanna Darula, Katalin F Medzihradszky, József Maléth, Péter Hegyi, Stephan Sigrist, József Mihály
Regulation of the cytoskeleton is fundamental to the development and functioning of synaptic terminals, such as neuromuscular junctions. Nevertheless, despite identification of numerous proteins that regulate synaptic actin and microtubule dynamics, the mechanisms of cytoskeletal control during terminal arbor formation has remained largely elusive. Here, we show that DAAM, a member of the formin family of cytoskeleton organizing factors, is an important presynaptic regulator of neuromuscular junction development in Drosophila We demonstrate that the actin filament assembly activity of DAAM plays a negligible role in terminal formation; rather, DAAM is necessary for synaptic microtubule organization...
February 27, 2018: Development
Michela Manni, Sanjay Gupta, Edd Ricker, Yurii Chinenov, Sung Ho Park, Man Shi, Tania Pannellini, Rolf Jessberger, Lionel B Ivashkiv, Alessandra B Pernis
Age-associated B cells (ABCs) are a subset of B cells dependent on the transcription factor T-bet that accumulate prematurely in autoimmune settings. The pathways that regulate ABCs in autoimmunity are largely unknown. SWAP-70 and DEF6 (also known as IBP or SLAT) are the only two members of the SWEF family, a unique family of Rho GTPase-regulatory proteins that control both cytoskeletal dynamics and the activity of the transcription factor IRF4. Notably, DEF6 is a newly identified human risk variant for systemic lupus erythematosus...
February 26, 2018: Nature Immunology
Shin-Young Park, Joong-Soo Han
Phospholipase D1 (PLD1) is generally accepted as playing an important role in the regulation of multiple cell functions, such as cell growth, survival, differentiation, membrane trafficking, and cytoskeletal organization. Recent findings suggest that PLD1 also plays an important role in the regulation of neuronal differentiation of neuronal cells. Moreover, PLD1-mediated signaling molecules dynamically regulate the neuronal differentiation of neural stem cells (NSCs). Rho family GTPases and Ca2+ -dependent signaling, in particular, are closely involved in PLD1-mediated neuronal differentiation of NSCs...
February 24, 2018: Journal of Molecular Neuroscience: MN
Thomas O'Loughlin, Thomas A Masters, Folma Buss
The intracellular functions of myosin motors requires a number of adaptor molecules, which control cargo attachment, but also fine-tune motor activity in time and space. These motor-adaptor-cargo interactions are often weak, transient or highly regulated. To overcome these problems, we use a proximity labelling-based proteomics strategy to map the interactome of the unique minus end-directed actin motor MYO6. Detailed biochemical and functional analysis identified several distinct MYO6-adaptor modules including two complexes containing RhoGEFs: the LIFT (LARG-Induced F-actin for Tethering) complex that controls endosome positioning and motility through RHO-driven actin polymerisation; and the DISP (DOCK7-Induced Septin disPlacement) complex, a novel regulator of the septin cytoskeleton...
February 21, 2018: EMBO Reports
Alexia Vite, Caimei Zhang, Roslyn Yi, Sabrina Emms, Glenn L Radice
Shortly after birth, muscle cells of the mammalian heart lose their ability to divide. At the same time, the N-cadherin/catenin cell adhesion complex accumulates at the cell termini creating a specialized type of cell-cell contact called the intercalated disc (ICD). To investigate the relationship between ICD maturation and proliferation, αE-catenin ( Ctnna1 ) and αT-catenin ( Ctnna3 ) genes were deleted to generate cardiac-specific α-catenin double knockout (DKO) mice. DKO mice exhibited aberrant N-cadherin expression, mislocalized actomyosin activity, and increased cardiomyocyte proliferation that was dependent on Yap activity...
February 21, 2018: Development
Mark W Majesky
The vascular system forms as a branching network of endothelial cells that acquire identity as arterial, venous, hemogenic, or lymphatic. Endothelial specification depends on gene targets transcribed by Ets domain-containing factors, including Ets variant gene 2 (Etv2), together with the activity of chromatin-remodeling complexes containing Brahma-related gene-1 (Brg1). Once specified and assembled into vessels, mechanisms regulating lumen diameter and axial growth ensure that the structure of the branching vascular network matches the need for perfusion of target tissues...
March 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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