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activity-regulated cytoskeletal

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https://www.readbyqxmd.com/read/29788979/marcks-and-marcks-like-proteins-in-development-and-regeneration
#1
REVIEW
Mohamed El Amri, Una Fitzgerald, Gerhard Schlosser
BACKGROUND: The Myristoylated Alanine-Rich C-kinase Substrate (MARCKS) and MARCKS-like protein 1 (MARCKSL1) have a wide range of functions, ranging from roles in embryonic development to adult brain plasticity and the inflammatory response. Recently, both proteins have also been identified as important players in regeneration. Upon phosphorylation by protein kinase C (PKC) or calcium-dependent calmodulin-binding, MARCKS and MARCKSL1 translocate from the membrane into the cytosol, modulating cytoskeletal actin dynamics and vesicular trafficking and activating various signal transduction pathways...
May 22, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29780159/modulation-of-store-operated-calcium-entry-and-nascent-adhesion-by-p21-activated-kinase-1
#2
In-Sook Jeon, Hye-Ryun Kim, Eun-Young Shin, Eung-Gook Kim, Heon-Seok Han, Jin-Tae Hong, Hak-Kyo Lee, Ki-Duk Song, Joong-Kook Choi
Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE)...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29768467/alpha-7-nicotinic-receptors-attenuate-neurite-development-through-calcium-activation-of-calpain-at-the-growth-cone
#3
Justin R King, Nadine Kabbani
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth...
2018: PloS One
https://www.readbyqxmd.com/read/29759483/induction-of-the-immunoproteasome-subunit-lmp7-links-proteostasis-and-immunity-in-%C3%AE-synuclein-aggregation-disorders
#4
Scott Ugras, Malcolm J Daniels, Hossein Fazelinia, Neal S Gould, Anastasia K Yocum, Kelvin C Luk, Esteban Luna, Hua Ding, Chris McKennan, Steven Seeholzer, Dan Martinez, Perry Evans, Daniel Brown, John E Duda, Harry Ischiropoulos
Accumulation of aggregated α-synuclein into Lewy bodies is thought to contribute to the onset and progression of dopaminergic neuron degeneration in Parkinson's disease (PD) and related disorders. Although protein aggregation is associated with perturbation of proteostasis, how α-synuclein aggregation affects the brain proteome and signaling remains uncertain. In a mouse model of α-synuclein aggregation, 6% of 6215 proteins and 1.6% of 8183 phosphopeptides changed in abundance, indicating conservation of proteostasis and phosphorylation signaling...
May 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29757266/spatial-and-temporal-control-of-t-cell-activation-using-a-photoactivatable-agonist
#5
Elisa Sanchez, Morgan Huse
T lymphocytes engage in rapid, polarized signaling, occurring within minutes following TCR activation. This induces formation of the immunological synapse, a stereotyped cell-cell junction that regulates T cell activation and directionally targets effector responses. To study these processes effectively, an imaging approach that is tailored to capturing fast, polarized responses is necessary. This protocol describes such a system, which is based on a photoactivatable peptide-major histocompatibility complex (pMHC) that is non-stimulatory until it is exposed to ultraviolet light...
April 25, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29755318/arc-3-utr-splicing-leads-to-dual-and-antagonistic-effects-in-fine-tuning-arc-expression-upon-bdnf-signaling
#6
Chiara Paolantoni, Simona Ricciardi, Veronica De Paolis, Chinenye Okenwa, Caterina Catalanotto, Maria T Ciotti, Antonino Cattaneo, Carlo Cogoni, Corinna Giorgi
Activity-regulated cytoskeletal associated protein (Arc) is an immediate-early gene critically involved in synaptic plasticity and memory consolidation. Arc mRNA is rapidly induced by synaptic activation and a portion is locally translated in dendrites where it modulates synaptic strength. Being an activity-dependent effector of homeostatic balance, regulation of Arc is uniquely tuned to result in short-lived bursts of expression. Cis -Acting elements that control its transitory expression post-transcriptionally reside primarily in Arc mRNA 3' UTR...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29754437/reduced-fiber-size-capillary-supply-and-mitochondrial-activity-in-constitutional-thinness-skeletal-muscle
#7
Bogdan Galusca, Julien Verney, Emmanuelle Meugnier, Yiin Ling, Pascal Edouard, Leonard Feasson, Marion Ravelojaona, Hubert Vidal, Bruno Estour, Natacha Germain
AIM: Constitutional thinness (CT) is a rare condition of natural low bodyweight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison to a normal BMI control group. METHODS: 10 CT women (BMI< 17.5 kg/m2) and 10 female controls (BMI: 18.5-25 kg/m2) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibers pattern, capillarity, enzymes activities and transcriptomics...
May 13, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29753725/ca-2-signaling-and-src-kinases-controlled-cellular-functions
#8
REVIEW
Estefanía Anguita, Antonio Villalobo
Calcium-mediated signaling and the functionality of Src-family tyrosine kinases (SFKs) are two interconnected processes. Activation of these kinases, which are coupled to a series of receptors, mediates Ca2+ mobilization by regulating Ca2+ channels, and the generated Ca2+ signal in turn exerts control on the kinase activity via calmodulin. In this review, we shall cover the regulation of selected processes where crosstalk between the functionality of SFKs and the Ca2+ signal occurs during the lifespan of the cell, when subjected to different extracellular or intracellular stimuli...
May 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29747682/the-biology-and-role-of-cd44-in-cancer-progression-therapeutic-implications
#9
REVIEW
Chen Chen, Shujie Zhao, Anand Karnad, James W Freeman
CD44, a non-kinase transmembrane glycoprotein, is overexpressed in several cell types including cancer stem cells and frequently shows alternative spliced variants that are thought to play a role in cancer development and progression. Hyaluronan, the main ligand for CD44, binds to and activates CD44 resulting in activation of cell signaling pathways that induces cell proliferation, increases cell survival, modulates cytoskeletal changes, and enhances cellular motility. The different functional roles of CD44 standard (CD44s) and specific CD44 variant (CD44v) isoforms are not fully understood...
May 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29746086/activation-of-rho-family-gtpases-by-small-molecules
#10
Charuta C Palsuledesai, Zurab Surviladze, Anna Waller, T Fabiola Miscioscia, Yuna Guo, Yang Wu, Jake Strouse, Elsa Romero, Virginia M Salas, Ramona Curpan, Susan Young, Mark Carter, Terry Foutz, Zhanna Galochkina, Harold Ames, Mark K Haynes, Bruce S Edwards, Orazio Nicolotti, Li Luo, Oleg Ursu, Cristian G Bologa, Tudor I Oprea, Angela Wandinger-Ness, Larry A Sklar
Ras and Ras-related small GTPases are key regulators of diverse cellular functions that impact cell growth, survival, motility, morphogenesis and differentiation. They are important targets for studies of disease mechanisms as well as drug discovery. Here, we report the characterization of small molecule agonists of one or more of six Rho, Rab and Ras family GTPases that were first identified through flow cytometry based, multi-plexed high throughput screening of 200,000 compounds. The activators were categorized into three distinct chemical families that are represented by three lead compounds having the highest activity...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29739947/essential-role-of-linx-islr2-in-the-development-of-the-forebrain-anterior-commissure
#11
Shaniya Abudureyimu, Naoya Asai, Atsushi Enomoto, Liang Weng, Hiroki Kobayashi, Xiaoze Wang, Chen Chen, Shinji Mii, Masahide Takahashi
Linx is a member of the leucine-rich repeat and immunoglobulin family of membrane proteins which has critical roles in the development of the peripheral nervous system and forebrain connectivity. A previous study showed that Linx is expressed in projection neurons in the cortex and in cells that comprise the passage to the prethalamus that form the internal capsule, indicating the involvement of Linx in axon guidance and cell-cell communication. In this study, we found that Linx-deficient mice develop severe hydrocephalus and die perinatally by unknown mechanisms...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29734338/rit1-controls-actin-dynamics-via-complex-formation-with-rac1-cdc42-and-pak1
#12
Uta Meyer Zum Büschenfelde, Laura Isabel Brandenstein, Leonie von Elsner, Kristina Flato, Tess Holling, Martin Zenker, Georg Rosenberger, Kerstin Kutsche
RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1...
May 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29717064/glycerol-monolaurate-induces-filopodia-formation-by-disrupting-the-association-between-lat-and-slp-76-microclusters
#13
Michael S Zhang, Phuong M Tran, Alexander J Wolff, Mikaela M Tremblay, Micaela G Fosdick, Jon C D Houtman
Glycerol monolaurate (GML) is a monoglyceride with potent antimicrobial properties that suppresses T cell receptor (TCR)-induced signaling and T cell effector function. Actin rearrangement is needed for the interaction of T cells with antigen-presenting cells and for migration to sites of infection. Because of the critical role actin rearrangement plays in T cell effector function, we analyzed the effect of GML on the rearrangement of the actin cytoskeleton after TCR activation. We found that GML-treated human T cells were less adherent than untreated T cells and did not form actin ring structures but instead developed numerous inappropriate actin-mediated filopodia...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29712777/palladin-is-a-neuron-specific-translational-target-of-mtor-signaling-that-regulates-axon-morphogenesis
#14
Yusuke Umegaki, Antonio Martinéz Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi
The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein Palladin, which is localized within the cell body and axons in hippocampal neurons...
April 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29699512/regulation-of-calretinin-in-malignant-mesothelioma-is-mediated-by-septin-7-binding-to-the-calb2-promoter
#15
Walter Blum, László Pecze, Janine Wörthmüller Rodriguez, Martine Steinauer, Beat Schwaller
BACKGROUND: The calcium-binding protein calretinin (gene name: CALB2) is currently considered as the most sensitive and specific marker for the diagnosis of malignant mesothelioma (MM). MM is a very aggressive tumor strongly linked to asbestos exposure and with no existing cure so far. The mechanisms of calretinin regulation, as well as its distinct function in MM are still poorly understood. METHODS: We searched for transcription factors binding to the CALB2 promoter and modulating calretinin expression...
April 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29698684/acidic-phe-regulates-cytoskeletal-dynamics-through-conformational-integrin-%C3%AE-1-activation-and-promotes-membrane-protrusion
#16
Shun Li, Niya Xiong, Yueting Peng, Kai Tang, Hongxia Bai, Xiaoying Lv, Ying Jiang, Xiang Qin, Hong Yang, Chunhui Wu, Peng Zhou, Yiyao Liu
An acidic extracellular pH (pHe) in the tumor microenvironment has been suggested to facilitate tumor growth and metastasis. However, the molecular mechanisms by which tumor cells sense acidic signal to induce a transition to an aggressive phenotype remain elusive. Here, we showed that an acidic pHe (pH 6.5) stimulation resulted in protrusion and epithelial-mesenchymal transition (EMT) of cancer cells, which promoted migration and matrix degeneration. Using computational molecular dynamics simulations, we reported acidic pHe-induced opening of the Integrin dimers (α5β1) headpiece which indicated the activation of integrin...
April 23, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29692731/differential-toxicity-of-mdia-formin-directed-functional-agonists-and-antagonists-in-developing-zebrafish
#17
Hunter LeCorgne, Andrew M Tudosie, Kari Lavik, Robin Su, Kathryn N Becker, Sara Moore, Yashna Walia, Alexander Wisner, Daniel Koehler, Arthur S Alberts, Frederick E Williams, Kathryn M Eisenmann
The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29684587/trpm7-controls-mesenchymal-features-of-breast-cancer-cells-by-tensional-regulation-of-sox4
#18
Arthur J Kuipers, Jeroen Middelbeek, Kirsten Vrenken, Carlos Pérez-González, Geert Poelmans, Jeffrey Klarenbeek, Kees Jalink, Xavier Trepat, Frank N van Leeuwen
Mechanically induced signaling pathways are important drivers of tumor progression. However, if and how mechanical signals affect metastasis or therapy response remains poorly understood. We previously found that the channel-kinase TRPM7, a regulator of cellular tension implicated in mechano-sensory processes, is required for breast cancer metastasis in vitro and in vivo. Here, we show that TRPM7 contributes to maintaining a mesenchymal phenotype in breast cancer cells by tensional regulation of the EMT transcription factor SOX4...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29682742/rac-gtpases-and-rac-gefs-in-neutrophil-adhesion-migration-and-recruitment
#19
REVIEW
Chiara Pantarelli, Heidi C E Welch
Rac-GTPases and their Rac-GEF activators play important roles in the recruitment and host defense functions of neutrophils. These proteins control the activation of adhesion molecules and the cytoskeletal dynamics that enable the adhesion, migration and tissue recruitment of neutrophils. They also regulate the effector functions that allow neutrophils to kill bacterial and fungal pathogens, and to clear debris. This review focusses on the roles of Rac-GTPases and Rac-GEFs in neutrophil adhesion, migration and recruitment...
April 23, 2018: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29675452/attaching-and-effacing-pathogens-exploit-junction-regulatory-activities-of-n-wasp-and-snx9-to-disrupt-the-intestinal-barrier
#20
John J Garber, Emily M Mallick, Karen M Scanlon, Jerrold R Turner, Michael S Donnenberg, John M Leong, Scott B Snapper
Background & Aims: Neural Wiskott-Aldrich Syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton in epithelial tissues and is poised to mediate cytoskeletal-dependent aspects of apical junction complex (AJC) homeostasis. Attaching-and-effacing (AE) pathogens disrupt this homeostasis through translocation of the effector molecule early secreted antigenic target-6 (ESX)-1 secretion-associated protein F (EspF). Although the mechanisms underlying AJC disruption by EspF are unknown, EspF contains putative binding sites for N-WASP and the endocytic regulator sorting nexin 9 (SNX9)...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
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