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https://www.readbyqxmd.com/read/28921928/inverted-formins-a-sub-family-of-atypical-formins
#1
REVIEW
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 sub-family 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
https://www.readbyqxmd.com/read/28914606/nanoscale-architecture-of-the-schizosaccharomyces-pombe-contractile-ring
#2
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
https://www.readbyqxmd.com/read/28889942/differential-functions-of-wave-regulatory-complex-subunits-in-the-regulation-of-actin-driven-processes
#3
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
https://www.readbyqxmd.com/read/28877993/stabilization-of-dynamic-microtubules-by-mdia1-drives-tau-dependent-a%C3%AE-1-42-synaptotoxicity
#4
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...
September 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28852060/fmnl2-and-3-regulate-golgi-architecture-and-anterograde-transport-downstream-of-cdc42
#5
Frieda Kage, Anika Steffen, Adolf Ellinger, Carmen Ranftler, Christian Gehre, Cord Brakebusch, Margit Pavelka, Theresia Stradal, Klemens Rottner
The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly factors established to regulate cell edge protrusion during migration and invasion. Here we report these formins to additionally accumulate and function at the Golgi apparatus. As opposed to lamellipodia, Golgi targeting of these proteins required both their N-terminal myristoylation and the interaction with Cdc42...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852021/evolutionary-conserved-role-of-eukaryotic-translation-factor-eif5a-in-the-regulation-of-actin-nucleating-formins
#6
Verónica Muñoz-Soriano, Ana Domingo-Muelas, Tianlu Li, Esther Gamero, Alexandra Bizy, Isabel Fariñas, Paula Alepuz, Nuria Paricio
Elongation factor eIF5A is required for the translation of consecutive prolines, and was shown in yeast to translate polyproline-containing Bni1, an actin-nucleating formin required for polarized growth during mating. Here we show that Drosophila eIF5A can functionally replace yeast eIF5A and is required for actin-rich cable assembly during embryonic dorsal closure (DC). Furthermore, Diaphanous, the formin involved in actin dynamics during DC, is regulated by and mediates eIF5A effects. Finally, eIF5A controls cell migration and regulates Diaphanous levels also in mammalian cells...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817833/fmnl2-destabilises-commd10-to-activate-nf-%C3%AE%C2%BAb-pathway-in-invasion-and-metastasis-of-colorectal-cancer
#7
S S Yang, X M Li, M Yang, X L Ren, J L Hu, X H Zhu, F F Wang, Z C Zeng, J Y Li, Z Q Cheng, W T Liao, Y Q Ding, J Guan, L Liang
BACKGROUND: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. METHODS: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28803703/viral-hijacking-of-formins-in-neurodevelopmental-pathologies
#8
REVIEW
Karen Racicot, Sarah VanOeveren, Art Alberts
The 2015 Zika virus (ZIKV) outbreak caused global concern when it was determined to cause microcephaly, hearing loss, and other neurodevelopmental manifestations upon fetal exposure. Significant progress has been made in our understanding of the interactions between ZIKV and the pregnant host, but there is still a critical need to understand how ZIKV and other neurotropic viruses affect fetal neurodevelopment. Diaphanous-related formins (Diaphs) have recently been identified as microcephaly-associated proteins in humans and mice...
August 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#9
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28795316/diaph3-promoted-the-growth-migration-and-metastasis-of-hepatocellular-carcinoma-cells-by-activating-beta-catenin-tcf-signaling
#10
Li Dong, Zhijun Li, Liying Xue, Gang Li, Cuiying Zhang, Zhihui Cai, Hui Li, Ruifang Guo
The enhanced ability of cancer cell migration and metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Diaphanous-related formin 3 (DIAPH3) has been reported to regulate the motility of cells by remodeling the cytoskeleton. However, the mechanism through which DIAPH3 regulated the motility of cancer cells remains largely unknown. In this study, we have shown that the expression of DIAPH3 was up-regulated in HCC...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28774893/mrtf-transcription-and-ezrin-dependent-plasma-membrane-blebbing-are-required-for-entotic-invasion
#11
Laura Soto Hinojosa, Manuel Holst, Christian Baarlink, Robert Grosse
Entosis is a nonapoptotic form of cell death initiated by actomyosin-dependent homotypic cell-in-cell invasion that can be observed in malignant exudates during tumor progression. We previously demonstrated formin-mediated actin dynamics at the rear of the invading cell as well as nonapoptotic plasma membrane (PM) blebbing in this cellular motile process. Although the contractile actin cortex involved in bleb-driven motility is well characterized, a role for transcriptional regulation in this process has not been studied...
August 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28768717/formin-2-links-neuropsychiatric-phenotypes-at-young-age-to-an-increased-risk-for-dementia
#12
Roberto Carlos Agís-Balboa, Paulo Pinhero, Nelson Rebola, Cemil Kerimoglu, Eva Benito, Michael Gertig, Sanaz Bahari-Javan, Gaurav Jain, Susanne Burkhardt, Ivana Delalle, Alexander Jatzko, Markus Dettenhofer, Patricia A Zunszain, Andrea Schmitt, Peter Falkai, Julius C Pape, Elisabeth B Binder, Christophe Mulle, Andre Fischer, Farahnaz Sananbenesi
Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer's disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity, while the consolidation of new memories is unaffected...
August 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28760985/distinct-functions-of-diaphanous-related-formins-regulate-hiv-1-uncoating-and-transport
#13
Michael Keegan Delaney, Viacheslav Malikov, Qingqing Chai, Guangyuan Zhao, Mojgan H Naghavi
Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by controlling actin nucleation and microtubule (MT) stabilization to facilitate processes such as cell polarization and migration; yet the full extent of their activities remains unknown. Here, we uncover two discrete roles and functions of DRFs during early human immunodeficiency virus type 1 (HIV-1) infection. Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1-induced MT stabilization and the intracellular motility of virus particles...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28747699/osfh15-a-class-i-formin-interacts-with-microfilaments-and-microtubules-to-regulate-grain-size-via-affecting-cell-expansion-in-rice
#14
Tiantian Sun, Shanwei Li, Haiyun Ren
Grain size is an important agronomic trait determining rice yield and is mainly restricted by spikelet hull size. However, it remains largely unknown how the spikelet hull size is regulated. In this study, OsFH15, a class I formin protein in Oryza sativa, was found to be able to regulate the size of cells and spikelet hull. OsFH15-Cas9 and OsFH15-RNAi mutants had decreased grain size with reduced cell length, cell width and cell area of inner epidermal cells of the lemma compared with wild-type plants. By contrast, OsFH15-overexpressed plants had increased grain size with larger cells, as well as more abundant microtubules (MTs) and actin filaments (AFs) arrays...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746856/biphasic-effect-of-profilin-impacts-the-formin-mdia1-force-sensing-mechanism-in-actin-polymerization
#15
Hiroaki Kubota, Makito Miyazaki, Taisaku Ogawa, Togo Shimozawa, Kazuhiko Kinosita, Shin'ichi Ishiwata
Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre- and posttranslocated states of the formin homology domain two dimer...
July 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28744815/mammalian-diaphanous-related-formin-1-restricts-early-phases-of-influenza-a-nws-33-virus-h1n1-infection-in-llc-mk2-cells-by-affecting-cytoskeleton-dynamics
#16
Flora De Conto, Alessandra Fazzi, Sergey V Razin, Maria Cristina Arcangeletti, Maria Cristina Medici, Silvana Belletti, Carlo Chezzi, Adriana Calderaro
Viruses depend on cellular machinery to efficiently replicate. The host cytoskeleton is one of the first cellular systems hijacked by viruses in order to ensure their intracellular transport and promote the development of infection. Our previous results demonstrated that stable microfilaments and microtubules interfered with human influenza A/NWS/33 virus (H1N1) infection in semi-permissive LLC-MK2 cells. Although formins play a key role in cytoskeletal remodelling, few studies addressed a possible role of these proteins in development of viral infection...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28708292/fhod1-regulates-cytoplasmic-actin-based-spindle-migration-for-mouse-oocyte-asymmetric-cell-division
#17
Meng-Hao Pan, Fei Wang, Yujie Lu, Feng Tang, Xing Duan, Yu Zhang, Bo Xiong, Shao-Chen Sun
FHOD1 is a member of Diaphanous-related formins (DRFs) which belongs to the Formin family. Previous studies have shown that the DFRs might affect several cellular functions such as morphogenesis, cytokinesis, cell polarity, and embryonic differentiation. However, there is no evidence showing the functions of FHOD1 during oocyte meiosis. This study is aimed at exploring the roles of FHOD1 during the mammalian oocyte maturation. Immunofluorescent staining showed that FHOD1 was restricted to the nucleus in germinal vesicle (GV) stage of the oocytes, after the GV breakdown FHOD1 was primarily located at two poles of the spindle at both metaphases I and II stages...
July 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28691087/cytoskeletal-actin-dynamics-shape-a-ramifying-actin-network-underpinning-immunological-synapse-formation
#18
Marco Fritzsche, Ricardo A Fernandes, Veronica T Chang, Huw Colin-York, Mathias P Clausen, James H Felce, Silvia Galiani, Christoph Erlenkämper, Ana M Santos, John M Heddleston, Isabela Pedroza-Pacheco, Dominic Waithe, Jorge Bernardino de la Serna, B Christoffer Lagerholm, Tsung-Li Liu, Teng-Leong Chew, Eric Betzig, Simon J Davis, Christian Eggeling
T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28682694/daam1-regulates-fascin-for-actin-assembly-in-mouse-oocyte-meiosis
#19
Yujie Lu, Yu Zhang, Meng-Hao Pan, Nam-Hyung Kim, Shao-Chen Sun, Xiang-Shun Cui
As a formin protein, Daam1 (Dishevelled-associated activator of morphogenesis 1) is reported to regulate series of cell processes like endocytosis, cell morphology and migration via its effects on actin assembly in mitosis. However, whether Daam1 plays roles in female meiosis remains uncertain. In this study, we investigated the expression and functions of Daam1 during mouse oocyte meiosis. Our results indicated that Daam1 localized at the cortex of oocytes, which was similar with actin filaments. After Daam1 morpholino (MO) microinjection, the expression of Daam1 significantly decreased, which resulted in the failure of oocyte polar body extrusion...
July 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28674019/changes-in-e-cadherin-rigidity-sensing-regulate-cell-adhesion
#20
Caitlin Collins, Aleksandra K Denisin, Beth L Pruitt, W James Nelson
Mechanical cues are sensed and transduced by cell adhesion complexes to regulate diverse cell behaviors. Extracellular matrix (ECM) rigidity sensing by integrin adhesions has been well studied, but rigidity sensing by cadherins during cell adhesion is largely unexplored. Using mechanically tunable polyacrylamide (PA) gels functionalized with the extracellular domain of E-cadherin (Ecad-Fc), we showed that E-cadherin-dependent epithelial cell adhesion was sensitive to changes in PA gel elastic modulus that produced striking differences in cell morphology, actin organization, and membrane dynamics...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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