Article

Building distinct actin filament networks in a common cytoplasm.

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
Current biology: CB (Impact Factor: 10.99). 07/2011; 21(14):R560-9. DOI: 10.1016/j.cub.2011.06.019
Source: PubMed

ABSTRACT Eukaryotic cells generate a diversity of actin filament networks in a common cytoplasm to optimally perform functions such as cell motility, cell adhesion, endocytosis and cytokinesis. Each of these networks maintains precise mechanical and dynamic properties by autonomously controlling the composition of its interacting proteins and spatial organization of its actin filaments. In this review, we discuss the chemical and physical mechanisms that target distinct sets of actin-binding proteins to distinct actin filament populations after nucleation, resulting in the assembly of actin filament networks that are optimized for specific functions.

0 Bookmarks
 · 
105 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Connexin43 (Cx43) has roles in cell-cell communication as well as channel independent roles in regulating motility and migration. Loss of function approaches to decrease Cx43 protein levels in neural cells result in reduced migration of neurons during cortical development in mice and impaired glioma tumor cell migration. In other cell types, correlations between Cx43 expression and cell morphology, adhesion, motility and migration have been noted. In this review we will discuss the common themes that have been revealed by a detailed comparison of the published results of neuronal cells with that of other cell types. In brief, these comparisons clearly show differences in the stability and directionality of protrusions, polarity of movement, and migration, depending on whether a) residual Cx43 levels remain after siRNA or shRNA knockdown, b) Cx43 protein levels are not detectable as in cells from Cx43(-/-) knockout mice or in cells that normally have no endogenous Cx43 expression, c) gain-of-function approaches are used to express Cx43 in cells that have no endogenous Cx43 and, d) Cx43 is over-expressed in cells that already have low endogenous Cx43 protein levels. What is clear from our comparisons is that Cx43 expression influences the adhesiveness of cells and the directionality of cellular processes. These observations are discussed in light of the ability of cells to rearrange their cytoskeleton and move in an organized manner. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions (Pt II).
    Biochimica et Biophysica Acta 05/2012; · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adherens junctions and desmosomes interface the cytoskeletons of adjacent cells into a mechanical syncitium. In doing so, intercellular junctions endow tissues with the strength needed to sustain mechanical stresses encountered in normal physiology and coordinate tension during morphogenesis. Though much is known about the biological mechanisms underlying junction formation, little is known about how tissue-scale mechanical properties are established. Here, we use deep AFM indentation to measure the apparent stiffness of epithelial monolayers reforming from dissociated cells and examine which cellular processes give rise to tissue-scale mechanics. We show that the formation of intercellular junctions coincided with an increase in the apparent stiffness of reforming monolayers that reflected the generation of a tissue-level tension. Tension rapidly increased reaching a maximum after 150 minutes before settling to a lower level over the next three hours as monolayers reached homeostasis. The emergence of tissue tension correlated with the formation of adherens junctions but not desmosomes. As a consequence, inhibition of any of the molecular mechanisms participating in adherens junction initiation, remodelling, and maturation significantly impeded the emergence of tissue-level tension in monolayers.
    Journal of Cell Science 03/2014; · 5.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The contractile actin cortex is a thin layer of actin, myosin, and actin-binding proteins that subtends the membrane of animal cells. The cortex is the main determinant of cell shape and plays a fundamental role in cell division [1-3], migration [4], and tissue morphogenesis [5]. For example, cortex contractility plays a crucial role in amoeboid migration of metastatic cells [6] and during division, where its misregulation can lead to aneuploidy [7]. Despite its importance, our knowledge of the cortex is poor, and even the proteins nucleating it remain unknown, though a number of candidates have been proposed based on indirect evidence [8-15]. Here, we used two independent approaches to identify cortical actin nucleators: a proteomic analysis using cortex-rich isolated blebs, and a localization/small hairpin RNA (shRNA) screen searching for phenotypes with a weakened cortex or altered contractility. This unbiased study revealed that two proteins generated the majority of cortical actin: the formin mDia1 and the Arp2/3 complex. Each nucleator contributed a similar amount of F-actin to the cortex but had very different accumulation kinetics. Electron microscopy examination revealed that each nucleator affected cortical network architecture differently. mDia1 depletion led to failure in division, but Arp2/3 depletion did not. Interestingly, despite not affecting division on its own, Arp2/3 inhibition potentiated the effect of mDia1 depletion. Our findings indicate that the bulk of the actin cortex is nucleated by mDia1 and Arp2/3 and suggest a mechanism for rapid fine-tuning of cortex structure and mechanics by adjusting the relative contribution of each nucleator.
    Current Biology 07/2014; 24(14):1628. · 9.49 Impact Factor

Full-text (2 Sources)

View
25 Downloads
Available from
Jun 5, 2014