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First published online 7 February 2007
doi: 10.1242/dev.000513

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Acto-myosin reorganization and PAR polarity in C. elegans

¹ Research Institute for Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
² Max Planck Institute - Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.

View larger version (79K): [in this window] [in a new window]   Fig. 1. Contraction of acto-myosin networks. Actin filaments (green) and myosin filaments (orange) interact to generate contractility. (A-C) Large boxes illustrate the structure of the acto-myosin network; small boxes illustrate the overall network before (top) and after (bottom) contraction. The black arrows indicate a contractile stimulus, for instance, ATP addition. Muscle sarcomeres (A) are highly ordered and contract uniformly. (B) Cortical networks are randomly organized; contraction results in local densities of contractility and local breaks in the network. (C) Contractile interactions do not exist in a solated network. (D) A uniform acto-myosin network (as depicted in B) exhibits local contractions throughout the network (left box), but the local downregulation of myosin activity or the severing of actin filaments (circle, left box) can lead to a global asymmetric contraction of the entire network (right box).

View larger version (44K): [in this window] [in a new window]   Fig. 2. Cortical polarity in one-cell C. elegans embryos. (A-F) Illustrations of aspects (see key) of C. elegans embryos as they change from entry into the first cell cycle (left), to the completion of polarity establishment (right), a period of about eight minutes. The approximate timing of events relative to entry into the first cell cycle is shown in the upper bar. Cortical activity is indicated by the gray outline of the embryos; contractility is indicated by the cortical ingressions. The identity of the proteins or complexes depicted is indicated in the key. The acto-myosin network in C is indicated from a surface view of the embryo cortex; other proteins and centrosomes are shown in the embryo mid-plane. Embryo anterior is to the left. The complete kinetics of RhoGAP CYK-4 localization (E) have not been investigated and thus are not depicted following the initiation of polarization.

View larger version (34K): [in this window] [in a new window]   Fig. 3. Establishing contractile polarity: Rho. (A-G) Illustrations of C. elegans embryos (E) depleted of Rho (RHO-1), (F) depleted of RhoGEF ECT-2, and (G) depleted of RhoGAP CYK-4, in comparison with (D) embryos lacking a contractile acto-myosin network and mutants of (B) posterior and (C) anterior PAR proteins. Embryo anterior, or the meiotic pole in D-G, is to the left. Rho and the acto-myosin network (pink) are required for contractile polarity. PAR polarity does not determine contractile polarity, although anterior PAR proteins such as PAR-6 modify contractility, and thus the respective sizes of the anterior and posterior domains are altered in par-3 mutants (C). (B) Contractile polarity can dictate anterior PAR polarity during polarity establishment in par-2 mutants, but thereafter PAR-2 is essential for maintaining anterior PAR polarity (not depicted). The acto-myosin network (pink) is indicated from a surface view of the embryo cortex; PAR-6 (red) is shown in the embryo mid-plane. (H-J) Diagrams of acto-myosin contractility regulation by Rho signaling. Arrows indicate positive regulation, although the precise molecular components involved have not been determined. (H) Without spatial or temporal regulation of Rho activity, `contractility' and `no contractility' compete. (I) In the anterior cortical domain, only RhoGEF ECT-2 is present, promoting contractility. (J) In the posterior cortical domain, only RhoGAP CYK-4 is present, eliminating contractility.

View larger version (21K): [in this window] [in a new window]   Fig. 4. Linking PAR polarity to contractile polarity: CDC-42. Illustrations of C. elegans embryos: (A) wild type; (B) depleted of CDC-42; (C) expressing a PAR-6-CRIB mutant; (D,E) depleted of Rho early (D) and late (E) in the first cell cycle. The acto-myosin network (pink) is indicated from a surface view of the embryo cortex; CDC-42 (purple dashed line) and PAR-6 (red) are shown in the embryo mid-plane. Embryo anterior, or the meiotic pole in C, is to the left. Embryos lacking CDC-42 or the CDC-42-binding CRIB domain of PAR-6 have reduced cortical localization of PAR-6, indicated by the dotted red line in B and C. Both PAR-6 and CDC-42 remain uniformly distributed around the cortex despite asymmetry of the acto-myosin network in rho-1(RNAi) embryos late in the cell cycle (E), suggesting that CDC-42 cannot respond to the acto-myosin network when Rho signaling is disrupted.

View larger version (31K): [in this window] [in a new window]   Fig. 5. A model of polarity establishment in one-cell C. elegans embryos. Illustrations of C. elegans embryos from fertilization (left) through to the initial phase of polarity establishment (right). Thin arrows indicate the temporal hierarchy of events. The identity of the proteins or complexes depicted is indicated in the key. The approximate timing of events relative to entry into the first cell cycle is shown in the upper bar. The acto-myosin network is indicated from a surface view of the embryo cortex; centrosome localization and the distribution of other proteins is shown in the mid-plane of embryos. Anterior, or the meiotic pole, is to the left. The events indicated are as follows, with numbers corresponding to those in the figure. (1) Fertilization, indicated by the thick black arrow, contributes centrosomes and RhoGAP CYK-4 to the oocyte. (2) CYK-4 localizes around the centrosomes and to a local cortical region. (3) Following entry into the cell cycle, RhoGEF ECT-2 becomes active throughout the cortex, leading to myosin activation via Rho•GTP and thus uniform contractility. (4) CDC-42 helps link the anterior PAR complex to the contractile cortex. (5) Centrosome assembly and RhoGAP CYK-4 activation provide a polarity establishment signal. (6) RhoGEF ECT-2 is eliminated from the cortex overlying the centrosomes. (7) Rho activity is downregulated in the local region, leading to downregulation of myosin activity and cessation of contractility. (8) The local region of non-contractility breaks the symmetry of the cortex and promotes a partial collapse of the acto-myosin network. (9) CDC-42 shrinks with the contractile domain, causing the anterior PAR complex to follow; RhoGEF ECT-2 and Rho shrink with the contractile domain. (10) RhoGEF ECT-2, RHO-1, CDC-42 and PAR-6 in the anterior domain promote contractility of the acto-myosin network, allowing for continued contraction of the anterior domain through a feedback loop.