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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
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
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
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 1, 2017: Current Biology: CB
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
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
Elham Ghorbanpour, Parvin Pasalar, Shahin Yazdani, Hamidreza Moazzeni, Elahe Elahi
PURPOSE: We aimed to assess whether the transcription factor PAX6 affects transcription of FMNL2. PAX6 is a transcription factor with significant roles in development of the eye and eye-related functions. FMNL2 encodes a member of the formin family of proteins and has roles in polymerization of actin and features of the cytoskeleton. The state of the cytoskeleton affects the flow of aqueous humor, disruption of which is a cornerstone of glaucoma pathology. METHODS: Initially, bioinformatics were used extensively to identify FMNL2 as an appropriate candidate gene for possible targeting by PAX6...
October 2017: Journal of Ophthalmic & Vision Research
Linxi Li, Elizabeth I Tang, Haiqi Chen, Qingquan Lian, Renshan Ge, Bruno Silvestrini, C Yan Cheng
The mechanism that regulates sperm release at spermiation is unknown. Herein, we utilized an animal model wherein rats were treated with adjudin, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide, via oral gavage to induce premature release of elongating/elongated spermatid, followed by round spermatids and spermatocytes. Spermatid release mimicking spermiation occurred within 6-12 h following adjudin treatment and by 96 h, virtually all tubules were devoid of spermatids. Using this model, we tracked the organization of F-actin and microtubules (MTs) by immunofluorescence microscopy, and the association of actin or MT regulatory proteins that either promote or demolish cytoskeletal integrity through changes in the organization of actin-microfilaments or MTs by co-immunoprecipitation...
October 12, 2017: Endocrinology
Can Zhang, Lin Wang, Jiaying Chen, Jie Liang, Yaming Xu, Zhe Li, Fuxue Chen, Dongshu Du
As the most common primary central nervous system tumor, glioma is characterized by high levels of mortality and migration. Unclear boundary with normal brain tissue results in poor treatment. The mammalian diaphanous-related formin 1 (Diaph1) which belongs to formin-homology protein family, is a target of RhoA and involved in a number of actin-related biological processes, which abnormally expressed in pathological conditions in a number of tumors. Immunohistochemical analysis showed that Diaph1 was overexpressed in glioma tissues compared with normal human brain tissue...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Dimitrios Vavylonis, Brandon G Horan
Formins polymerize actin filaments for the cytokinetic contractile ring. Using in vitro reconstitution of fission yeast contractile ring precursor nodes containing formins and myosin, a new study shows that formin-mediated polymerization is strongly inhibited upon the capture and pulling of actin filaments by myosin, a result that has broad implications for cellular mechanosensing.
October 9, 2017: Current Biology: CB
Nikolaos Parisis, Liliana Krasinska, Bethany Harker, Serge Urbach, Michel Rossignol, Alain Camasses, James Dewar, Nathalie Morin, Daniel Fisher
Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription...
November 2, 2017: EMBO Journal
David Pruyne
Formins are proteins that assist in regulating cytoskeletal organization through interactions with actin filaments and microtubules. Metazoans encode nine distinct formin subtypes based on sequence similarity, potentially allowing for great functional diversity for these proteins. Through the evolution of the eukaryotes, formins are believed to have repeatedly undergone rounds of gene duplications, followed by diversification and domain shuffling, but previous phylogenetic analyses have shed only a little light on the specific origins of different formin subtypes...
2017: PloS One
Katharina Rehklau, Lena Hoffmann, Christine B Gurniak, Martin Ott, Walter Witke, Luca Scorrano, Carsten Culmsee, Marco B Rust
Mitochondria form highly dynamic networks in which organelles constantly fuse and divide. The relevance of mitochondrial dynamics is evident from its implication in various human pathologies, including cancer or neurodegenerative, endocrine and cardiovascular diseases. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission that oligomerizes at the mitochondrial outer membrane and hydrolyzes GTP to drive mitochondrial fragmentation. Previous studies demonstrated that DRP1 recruitment and mitochondrial fission is promoted by actin polymerization at the mitochondrial surface, controlled by the actin regulatory proteins inverted formin 2 (INF2) and Spire1C...
October 5, 2017: Cell Death & Disease
Asuka Yuda, Christopher A McCulloch
The generation of cell extensions is critical for matrix remodeling in tissue invasion by cancer cells, but current methods for identifying molecules that regulate cell extension formation and matrix remodeling are not well adapted for screening purposes. We applied a grid-supported, floating collagen gel system (~100 Pa stiffness) to examine cell extension formation, collagen compaction, and collagen degradation in a single assay. With the use of cultured diploid fibroblasts, a fibroblast cell line, and two cancer cell lines, we found that compared with attached collagen gels (~2800 Pa), the mean number and length of cell extensions were respectively greater in the floating gels...
September 1, 2017: SLAS Discovery
Sathish Thiyagarajan, Shuyuan Wang, Ben O'Shaughnessy
During cytokinesis, a contractile actomyosin ring constricts and divides the cell in two. How the ring marshals actomyosin forces to generate tension is not settled. Recently, a superresolution microscopy study of the fission yeast ring revealed that myosins and formins that nucleate actin filaments colocalize in plasma membrane-anchored complexes called nodes in the constricting ring. The nodes move bidirectionally around the ring. Here we construct and analyze a coarse-grained mathematical model of the fission yeast ring to explore essential consequences of the recently discovered ring ultrastructure...
November 7, 2017: Molecular Biology of the Cell
Dennis Zimmermann, Kaitlin E Homa, Glen M Hocky, Luther W Pollard, Enrique M De La Cruz, Gregory A Voth, Kathleen M Trybus, David R Kovar
Cytokinesis physically separates dividing cells by forming a contractile actomyosin ring. The fission yeast contractile ring has been proposed to assemble by Search-Capture-Pull-Release from cytokinesis precursor nodes that include the molecular motor type-II myosin Myo2 and the actin assembly factor formin Cdc12. By successfully reconstituting Search-Capture-Pull in vitro, we discovered that formin Cdc12 is a mechanosensor, whereby myosin pulling on formin-bound actin filaments inhibits Cdc12-mediated actin assembly...
September 26, 2017: Nature Communications
Anna Hegsted, Curtis V Yingling, David Pruyne
Formins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one subfamily of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub-family in mammals, zebrafish, fruit flies, and worms...
September 16, 2017: Cytoskeleton
Nathan A McDonald, Abigail L Lind, Sarah E Smith, Rong Li, Kathleen Gould
The contractile ring is a complex molecular apparatus important for dividing many eukaryotic cells. Despite knowledge of its composition, the molecular architecture of the ring is not known. Here we applied super-resolution microscopy and FRET to determine the nanoscale spatial organization of Schizosaccharomyces pombe contractile ring components relative to the plasma membrane. As in other membrane-tethered actin structures, contractile ring proteins are stratified relative to the membrane. The lowest layer (0-80 nm) contains membrane-binding scaffolds, formin, and the myosin-II tail...
September 15, 2017: ELife
Christof Litschko, Joern Linkner, Stefan Brühmann, Theresia E B Stradal, Tobias Reinl, Lothar Jänsch, Klemens Rottner, Jan Faix
The WAVE regulatory complex (WRC) links upstream Rho-family GTPase signaling to the activation of the ARP2/3 complex in different organisms. WRC-induced and ARP2/3 complex-mediated actin nucleation beneath the plasma membrane is critical for actin assembly in the leading edge to drive efficient cell migration. The WRC is a stable heteropentamer composed of SCAR/WAVE, Abi, Nap, Pir and the small polypeptide Brk1/Hspc300. Functional interference with individual subunits of the complex frequently results in diminished amounts of the remaining polypeptides of the WRC complex, implying the complex to act as molecular entity...
September 4, 2017: European Journal of Cell Biology
Xiaoyi Qu, Feng Ning Yuan, Carlo Corona, Silvia Pasini, Maria Elena Pero, Gregg G Gundersen, Michael L Shelanski, Francesca Bartolini
Oligomeric Amyloid β1-42 (Aβ) plays a crucial synaptotoxic role in Alzheimer's disease, and hyperphosphorylated tau facilitates Aβ toxicity. The link between Aβ and tau, however, remains controversial. In this study, we find that in hippocampal neurons, Aβ acutely induces tubulin posttranslational modifications (PTMs) and stabilizes dynamic microtubules (MTs) by reducing their catastrophe frequency. Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects the synaptotoxicity and deficits of axonal transport induced by Aβ...
October 2, 2017: Journal of Cell Biology
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