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      Filopodia-like Actin Cables Position Nuclei in Association with Perinuclear Actin in Drosophila Nurse Cells

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      1 , 1 , 2 , 1 ,
      Developmental Cell
      Cell Press

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          Summary

          Controlling the position of the nucleus is vital for a number of cellular processes from yeast to humans. In Drosophila nurse cells, nuclear positioning is crucial during dumping, when nurse cells contract and expel their contents into the oocyte. We provide evidence that in nurse cells, continuous filopodia-like actin cables, growing from the plasma membrane and extending to the nucleus, achieve nuclear positioning. These actin cables move nuclei away from ring canals. When nurse cells contract, actin cables associate laterally with the nuclei, in some cases inducing nuclear turning so that actin cables become partially wound around the nuclei. Our data suggest that a perinuclear actin meshwork connects actin cables to nuclei via actin-crosslinking proteins such as the filamin Cheerio. We provide a revised model for how actin structures position nuclei in nurse cells, employing evolutionary conserved machinery.

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          Highlights

          • Actin cables in Drosophila nurse cells are unsegmented filopodia-like structures

          • E-cadherin is required for the orientation of actin cables toward the nucleus

          • Nuclear positioning is achieved by continuous elongation of actin cables

          • Actin cables associate with perinuclear actin-containing crosslinkers like filamin

          Abstract

          Huelsmann et al. propose a nuclear positioning model by visualizing the interplay between actin structures as Drosophila nurse cells contract to expel their contents. Filopodia-like actin cables grow from the plasma membrane, connect with an actin meshwork surrounding the nucleus, and push nuclei out of the path of cytoplasmic flow.

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          Most cited references54

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          Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain–like mechanism

          The actin cytoskeleton plays a fundamental role in various motile and morphogenetic processes involving membrane dynamics. We show that actin-binding proteins MIM (missing-in-metastasis) and IRSp53 directly bind PI(4,5)P2-rich membranes and deform them into tubular structures. This activity resides in the N-terminal IRSp53/MIM domain (IMD) of these proteins, which is structurally related to membrane-tubulating BAR (Bin/amphiphysin/Rvs) domains. We found that because of a difference in the geometry of the PI(4,5)P2-binding site, IMDs induce a membrane curvature opposite that of BAR domains and deform membranes by binding to the interior of the tubule. This explains why IMD proteins induce plasma membrane protrusions rather than invaginations. We also provide evidence that the membrane-deforming activity of IMDs, instead of the previously proposed F-actin–bundling or GTPase-binding activities, is critical for the induction of the filopodia/microspikes in cultured mammalian cells. Together, these data reveal that interplay between actin dynamics and a novel membrane-deformation activity promotes cell motility and morphogenesis.
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            Regulated Actin Cytoskeleton Assembly at Filopodium Tips Controls Their Extension and Retraction

            The extension and retraction of filopodia in response to extracellular cues is thought to be an important initial step that determines the direction of growth cone advance. We sought to understand how the dynamic behavior of the actin cytoskeleton is regulated to produce extension or retraction. By observing the movement of fiduciary marks on actin filaments in growth cones of a neuroblastoma cell line, we found that filopodium extension and retraction are governed by a balance between the rate of actin cytoskeleton assembly at the tip and retrograde flow. Both assembly and flow rate can vary with time in a single filopodium and between filopodia in a single growth cone. Regulation of assembly rate is the dominant factor in controlling filopodia behavior in our system.
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              Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables.

              During epithelial sheet formation, linear actin cables assemble at nascent adherens junctions. This process requires alpha-catenin and actin polymerization, although the underlying mechanism is poorly understood. Here, we show that formin-1 interacts with alpha-catenin, localizes to adherens junctions and nucleates unbranched actin filaments. Furthermore, disruption of the alpha-catenin-formin-1 interaction blocks assembly of radial actin cables and perturbs intercellular adhesion. A fusion protein of the beta-catenin-binding domain of alpha-catenin with the actin polymerization domains of formin-1 rescues formation of adherens junctions and associated actin cables in alpha-catenin-null keratinocytes. These findings provide new insight into how alpha-catenin orchestrates actin dynamics during intercellular junction formation.
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                Author and article information

                Journal
                Dev Cell
                Dev. Cell
                Developmental Cell
                Cell Press
                1534-5807
                1878-1551
                30 September 2013
                30 September 2013
                : 26
                : 6
                : 604-615
                Affiliations
                [1 ]Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
                [2 ]Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, FI-40014 Jyväskylä, Finland
                Author notes
                []Corresponding author nb117@ 123456cam.ac.uk
                Article
                S1534-5807(13)00483-8
                10.1016/j.devcel.2013.08.014
                3791400
                24091012
                dc994349-bbd9-4b96-b07a-7829e5cbbfd2
                © 2013 The Authors

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 14 November 2012
                : 18 June 2013
                : 17 August 2013
                Categories
                Article

                Developmental biology
                Developmental biology

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