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https://www.readbyqxmd.com/read/29343550/cdk1-dependent-phospho-inhibition-of-a-formin-f-bar-interaction-opposes-cytokinetic-contractile-ring-formation
#1
Alaina H Willet, K Adam Bohnert, Kathleen L Gould
In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12, localizes to the cell middle upon mitotic onset and nucleates the F-actin of the CR. Cdc12 medial recruitment is mediated in part by its direct binding to the F-BAR scaffold Cdc15. Given that Cdc12 is hyper-phosphorylated in M phase, we explored whether Cdc12 phospho-regulation impacts its association with Cdc15 during mitosis. We found that Cdk1, a major mitotic kinase, phosphorylates Cdc12 on six N-terminal residues near the Cdc15-binding site...
January 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29339084/mir-613-inhibits-cell-migration-and-invasion-by-downregulating-daam1-in-triple-negative-breast-cancer
#2
Huaping Xiong, Ting Yan, Weijie Zhang, Fangfang Shi, Xuesong Jiang, Xiaohua Wang, Shoushan Li, Ying Chen, Cheng Chen, Yichao Zhu
Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613...
January 12, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29328918/transmembrane-pickets-connect-cyto-and-pericellular-skeletons-forming-barriers-to-receptor-engagement
#3
Spencer A Freeman, Anthony Vega, Magdalena Riedl, Richard F Collins, Phillip P Ostrowski, Elliot C Woods, Carolyn R Bertozzi, Markku I Tammi, Diane S Lidke, Pauline Johnson, Satyajit Mayor, Khuloud Jaqaman, Sergio Grinstein
Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion, however, can be obstructed by transmembrane proteins ("pickets") that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44, an abundant transmembrane protein capable of indirect association with F-actin, hence likely to serve as a picket...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29323030/formin-bridges-between-microtubules-and-actin-filaments-in-axonal-growth-cones
#4
István Foldi, Szilárd Szikora, József Mihály
No abstract text is available yet for this article.
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321169/the-actin-mrtf-srf-transcriptional-circuit-controls-tubulin-acetylation-via-%C3%AE-tat1-gene-expression
#5
Jaime Fernández-Barrera, Miguel Bernabé-Rubio, Javier Casares-Arias, Laura Rangel, Laura Fernández-Martín, Isabel Correas, Miguel A Alonso
The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)-dependent transcription, which is known to be repressed by increased levels of G-actin...
January 10, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29296812/loss-of-mdia1-causes-neutropenia-via-attenuated-cd11b-endocytosis-and-increased-neutrophil-adhesion-to-the-endothelium
#6
Yang Mei, Gong Feng, Nina Rahimi, Baobing Zhao, Jingxin Zhang, Lan Cao, Jing Yang, Juehua Gao, Yihua Chen, Ronen Sumagin, William A Muller, Ling Zhang, Peng Ji
Formin protein mDia1 is involved in actin polymerization and plays important roles in the migration and adhesion of hematopoietic cells. The mDia1 encoding gene is located on chromosome 5q, which is commonly deleted in patients with del(5q) myelodysplastic syndromes (MDSs). We previously reported that mice with mDia1 deficiency developed neutropenia that closely mimics MDS. However, the mechanism of neutropenia in these mice and patients with del(5q) MDS remains incompletely defined. Here, we reveal that mDia1 knockout mice show cell-autonomously increased CD11b expression on neutrophils in the peripheral blood and bone marrow...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29282276/the-neuron-specific-formin-delphilin-nucleates-non-muscle-actin-but-does-not-enhance-elongation
#7
William T Silkworth, Kristina L Kunes, Grace C Nickel, Martin L Phillips, Margot E Quinlan, Christina L Vizcarra
The formin Delphilin binds the glutamate receptor, GluRδ2, in dendritic spines of Purkinje cells. Both proteins play a role in learning. To understand how Delphilin functions in neurons, we studied the actin assembly properties of this formin. Formins have a conserved formin homology 2 domain, which nucleates and associates with the fast growing end of actin filaments, influencing filament growth together with the formin homology 1 (FH1) domain. The strength of nucleation and elongation varies widely across formins...
December 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29259094/er-mitochondria-contacts-actin-dynamics-at-the-er-control-mitochondrial-fission-via-calcium-release
#8
Janos Steffen, Carla M Koehler
The formin-like protein INF2 is an important player in the polymerization of actin filaments. In this issue, Chakrabarti et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201709111) demonstrate that INF2 mediates actin polymerization at the endoplasmic reticulum (ER), resulting in increased ER-mitochondria contacts, calcium uptake by mitochondria, and mitochondrial division.
December 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29240780/filamina-and-formin2-regulate-skeletal-muscular-and-intestinal-formation-through-mesenchymal-progenitor-proliferation
#9
Gewei Lian, Sneha Kanaujia, Timothy Wong, Volney Sheen
The effects of actin dependent molecular mechanisms in coordinating cellular proliferation, migration and differentiation during embryogenesis are not well-understood. We have previously shown that actin-binding Filamin A (FlnA) and actin-nucleating Formin 2 (Fmn2) influence the development of the brain causing microcephaly in mice. In this study, we broaden this phenotype to explore the effects of these two proteins in the development of extra-CNS organ systems, including the gut, muscle, and skeleton. We observed defects in rib and sternum midline closure leading to thoracoabdominal schisis in FlnA+Fmn2 knockout mice, reminiscent of the pentalogy of Cantrell syndrome...
2017: PloS One
https://www.readbyqxmd.com/read/29239839/the-formin-diaph1-is-a-key-modulator-of-myocardial-ischemia-reperfusion-injury
#10
Karen M O'Shea, Radha Ananthakrishnan, Qing Li, Nosirudeen Quadri, Devi Thiagarajan, Gopalkrishna Sreejit, Lingjie Wang, Hylde Zirpoli, Juan Francisco Aranda, Arthur S Alberts, Ann Marie Schmidt, Ravichandran Ramasamy
The biochemical, ionic, and signaling changes that occur within cardiomyocytes subjected to ischemia are exacerbated by reperfusion; however, the precise mechanisms mediating myocardial ischemia/reperfusion (I/R) injury have not been fully elucidated. The receptor for advanced glycation end-products (RAGE) regulates the cellular response to cardiac tissue damage in I/R, an effect potentially mediated by the binding of the RAGE cytoplasmic domain to the diaphanous-related formin, DIAPH1. The aim of this study was to investigate the role of DIAPH1 in the physiological response to experimental myocardial I/R in mice...
November 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29191847/wasp-family-proteins-and-formins-compete-in-pseudopod-and-bleb-based-migration
#11
Andrew J Davidson, Clelia Amato, Peter A Thomason, Robert H Insall
Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal...
November 30, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29162803/mdia1-senses-both-force-and-torque-during-f-actin-filament-polymerization
#12
Miao Yu, Xin Yuan, Chen Lu, Shimin Le, Ryo Kawamura, Artem K Efremov, Zhihai Zhao, Michael M Kozlov, Michael Sheetz, Alexander Bershadsky, Jie Yan
Formins, an important family of force-bearing actin-polymerizing factors, function as homodimers that bind with the barbed end of actin filaments through a ring-like structure assembled from dimerized FH2 domains. It has been hypothesized that force applied to formin may facilitate transition of the FH2 ring from an inhibitory closed conformation to a permissive open conformation, speeding up actin polymerization. We confirm this hypothesis for mDia1 dependent actin polymerization by stretching a single-actin filament in the absence of profilin using magnetic tweezers, and observe that increasing force from 0...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158260/the-actin-organizing-formin-protein-fhod3-is-required-for-postnatal-development-and-functional-maintenance-of-the-adult-heart-in-mice
#13
Tomoki Ushijima, Noriko Fujimoto, Sho Matsuyama, Meikun Kan-O, Hiroshi Kiyonari, Go Shioi, Yohko Kage, Sho Yamasaki, Ryu Takeya, Hideki Sumimoto
Cardiac development and function require actin-myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that directs formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here, we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29158231/receptor-mediated-drp1-oligomerization-on-endoplasmic-reticulum
#14
Wei-Ke Ji, Rajarshi Chakrabarti, Xintao Fan, Lori Schoenfeld, Stefan Strack, Henry N Higgs
Drp1 is a dynamin guanosine triphosphatase important for mitochondrial and peroxisomal division. Drp1 oligomerization and mitochondrial recruitment are regulated by multiple factors, including interaction with mitochondrial receptors such as Mff, MiD49, MiD51, and Fis. In addition, both endoplasmic reticulum (ER) and actin filaments play positive roles in mitochondrial division, but mechanisms for their roles are poorly defined. Here, we find that a population of Drp1 oligomers is associated with ER in mammalian cells and is distinct from mitochondrial or peroxisomal Drp1 populations...
November 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29146911/cytokinesis-requires-localized-%C3%AE-actin-filament-production-by-an-actin-isoform-specific-nucleator
#15
A Chen, P D Arora, C A McCulloch, A Wilde
Cytokinesis is initiated by the localized assembly of the contractile ring, a dynamic actomyosin structure that generates a membrane furrow between the segregating chromosomal masses to divide a cell into two. Here we show that the stabilization and organization of the cytokinetic furrow is specifically dependent on localized β-actin filament assembly at the site of cytokinesis. β-actin filaments are assembled directly at the furrow by an anillin-dependent pathway that enhances RhoA-dependent activation of the formin DIAPH3, an actin nucleator...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142021/inf2-mediated-actin-polymerization-at-the-er-stimulates-mitochondrial-calcium-uptake-inner-membrane-constriction-and-division
#16
Rajarshi Chakrabarti, Wei-Ke Ji, Radu V Stan, Jaime de Juan Sanz, Timothy A Ryan, Henry N Higgs
Mitochondrial division requires division of both the inner and outer mitochondrial membranes (IMM and OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM division by recruitment of the dynamin Drp1, but effects on IMM division are not well characterized. We previously showed that actin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 recruitment in mammalian cells. Here, we show that INF2-mediated actin polymerization stimulates a second mitochondrial response independent of Drp1: a rise in mitochondrial matrix calcium through the mitochondrial calcium uniporter...
November 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29138824/genetic-mutational-testing-of-chinese-children-with-familial-hematuria-with-biopsy%C3%A2-proven-fsgs
#17
Yongzhen Li, Ying Wang, Qingnan He, Xiqiang Dang, Yan Cao, Xiaochuan Wu, Shuanghong Mo, Xiaoxie He, Zhuwen Yi
Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH)...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29129529/profilin-directly-promotes-microtubule-growth-through-residues-mutated-in-amyotrophic-lateral-sclerosis
#18
Jessica L Henty-Ridilla, M Angeles Juanes, Bruce L Goode
Profilin is an abundant actin monomer-binding protein with critical actin regulatory roles in vivo [1, 2]. However, profilin also influences microtubule dynamics in cells, which may be mediated in part through its interactions with formins that in turn bind microtubules [3, 4]. Specific residues on human profilin-1 (PFN1) are mutated in patients with amyotrophic lateral sclerosis (ALS) [5, 6]. However, the observation that some ALS-linked PFN1 mutants fail to alter cellular actin organization or dynamics [5-8] or in vitro actin-monomer affinity [9] has been perplexing, given that profilin is best understood as an actin regulator...
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29127202/drosophila-and-human-fhod-family-formins-nucleate-actin-filaments
#19
Aanand A Patel, Zeynep A Oztug Durer, Aaron P van Loon, Kathryn V Bremer, Margot E Quinlan
Formins are a conserved group of proteins that nucleate and processively elongate actin filaments. Among them, the formin homology domain-containing protein (FHOD) family of formins contributes to contractility of striated muscle and cell motility in several contexts. However, the mechanisms by which they carry out these functions remain poorly understood. Mammalian FHOD proteins were reported not to accelerate actin assembly in vitro; instead, they were proposed to act as barbed end cappers or filament bundlers...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29113947/diffusion-tensor-and-volumetric-magnetic-resonance-imaging-findings-in-the-brains-of-professional-musicians
#20
Niyazi Acer, Serap Bastepe-Gray, Ayse Sagiroglu, Kazim Z Gumus, Levent Degirmencioglu, Gokmen Zararsiz, Muhammet Usame Ozic
Professional musicians represent an ideal model to study the training-induced brain plasticity. The current study aimed to investigate the brain volume and diffusion characteristics of musicians using structural magnetic resonance and diffusion tensor imaging (DTI). The combined use of volumetric and diffusion methods in studying musician brain has not been done in literature. Our study group consisted of seven male musicians playing an instrument and seven age- and gender-matched non-musicians. We evaluated the volumes of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) and calculated total intracranial volume (TIV) and measured the fractional anisotropy (FA) of pre-selected WM bundles: corpus callosum (CC), corticospinal tract (CST), superior longitudinal fasciculus (SLF), forceps major (ForMaj), forceps minor (ForMin), and arcuate fasciculus (AF)...
November 4, 2017: Journal of Chemical Neuroanatomy
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