Cdc42 regulates junctional actin but not cell polarization in the <i>Caenorhabditis elegans</i> epidermis

Zilberman, Yuliya; Abrams, Joshua; Anderson, Dorian C.; Nance, Jeremy

doi:10.1083/jcb.201611061

Cited by 42 publications

(47 citation statements)

References 96 publications

(165 reference statements)

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“…In contrary, our studies showed that electrostatic binding to PI4P and PIP2 alone is sufficient to localize aPKC/Par-6 to the PM without interacting with additional proteins such as Cdc42. Our results are consistent with findings that removing Cdc42 in C. elegans late embryos or in Drosophila pupal epithelial cells does not severely disrupt aPKC and Par-6 localization (Georgiou et al, 2008;Zilberman et al, 2017). Although mechanisms governing the aPKC/Par-6 subcellular localization appear to be heavily cell-type specific and multi-layered, our results highlight that the electrostatic PM-binding property of aPKC needs to be taken into consideration when studying the protein regulators of aPKC/Par-6 subcellular localization.…”

Section: Electrostatic Binding To Phosphoinositides By Polybasic Psr supporting

confidence: 91%

A Polybasic Domain in aPKC Mediates Par6-Dependent Control of Membrane Targeting and Kinase Activity

Wei

Liu

Zhang

et al. 2019

Preprint

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Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for regulating cell polarization but remain to be fully elucidated. Unlike other members of the PKC family, aPKC has no well-defined or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein-protein interactions. Here we show that in both Drosophila and mammalian cells the pseudosubstrate region (PSr) of aPKC acts as a polybasic domain sufficient to target aPKC to the plasma membrane (PM) via electrostatic binding to PM phosphoinositides. PM-targeting of aPKC requires the physical interaction between the N-terminal PB1 domains in both aPKC and Par-6, which not only allosterically exposes PSr to PM-binding, but also inhibits aPKC kinase activity.Such kinase inhibition requires the C-terminal domain of Par-6 and can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a mechanism in which allosteric regulation of polybasic PSr in aPKC by Par-6 couples the control of both aPKC subcellular localization and spatial activation of its kinase activity.3

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Section: Electrostatic Binding To Phosphoinositides By Polybasic Psr supporting

confidence: 91%

A Polybasic Domain in aPKC Mediates Par6-Dependent Control of Membrane Targeting and Kinase Activity

Wei

Liu

Zhang

et al. 2019

Preprint

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“…Interestingly, we find that ABpl's anterior cell-cell contact shows significantly higher HMR-1/E-cadherin levels than the posterior, which can explain the observed anterior PAC-1 enrichment ( Figure 5E). We can only speculate that this asymmetric localization of PAC-1 might also contribute to enhanced levels of cell-cell contact F-actin and reinforce recruitment of cell-cell adhesion proteins as described for late stages of embryonic morphogenesis (Zilberman et al, 2017).…”

Section: Role Of Rho Gtpases and Their Regulators In Pcpsupporting

confidence: 53%

Planar cell polarity in the C. elegans embryo emerges by differential retention of aPARs at cell-cell contacts

Dutta

Odedra

Pohl

2019

Preprint

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Formation of the anteroposterior and dorsoventral body axis in the Caenorhabditis elegans embryo depends on cortical actomyosin flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization immediately after formation of cell-cell contacts is not fully understood.Here, we demonstrate that planar cell polarity (PCP) is established in the C. elegans embryo at the time of left-right (l/r) symmetry breaking. At this stage, centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) PAR-3, PAR-6 and PKC-3 from cell-cell contacts to the medial cortex, which results in their unmixing from apical myosin. Advection generally requires GSK-3 and CDC-42, while advection of PAR-6 specifically depends on the RhoGAP PAC-1. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1, PAC-1 and opposing retention of the antagonistic Wnt pathway components APC/APR-1 and Frizzled/MOM-5 at apical cell-cell contacts leads to planar asymmetries. The most obvious mark of PCP, asymmetric retention of PAR-3 at posterior cell-cell contacts on the left side of the embryo, is required for proper cytokinetic cell intercalation. Hence, our data uncover how PCP can be established through Wnt signaling as well as dissociation and planar asymmetric retention of aPARs mediated by distinct Rho GTPases and their regulators.

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“…Recent studies by several groups suggest that besides CED-10/ Rac1, the GTPases RHO-1 and CDC-42 also contribute to the morphogenetic process of ventral enclosure (Ouellette et al, 2016;Walck-Shannon et al, 2016;Wernike et al, 2016;Zilberman et al, 2017). However, cytoskeletal consequences of altering RHO-1 or CDC-42 function during ventral enclosure are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The RhoGAP HUM-7/Myo9 integrates signals to modulate RHO-1/RhoA during embryonic morphogenesis in Caenorhabditis elegans

et al. 2018

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During embryonic morphogenesis, cells and tissues undergo dramatic movements under the control of F-actin regulators. Our studies of epidermal cell migrations in developing Caenorhabditis elegans embryos have identified multiple plasma membrane signals that regulate the Rac GTPase, thus regulating WAVE and Arp2/3 complexes, to promote branched F-actin formation and polarized enrichment. Here, we describe a pathway that acts in parallel to Rac to transduce membrane signals to control epidermal F-actin through the GTPase RHO-1/RhoA. RHO-1 contributes to epidermal migration through effects on underlying neuroblasts. We identify signals to regulate RHO-1-dependent events in the epidermis. HUM-7, the C. elegans homolog of human MYO9A and MYO9B, regulates F-actin dynamics during epidermal migration. Genetics and biochemistry support that HUM-7 behaves as a GTPase-activating protein (GAP) for the RHO-1/RhoA and CDC-42 GTPases. Loss of HUM-7 enhances RHO-1-dependent epidermal cell behaviors. We identify SAX-3/ROBO as an upstream signal that contributes to attenuated RHO-1 activation through its regulation of HUM-7/Myo9. These studies identify a new role for RHO-1 during epidermal cell migration, and suggest that RHO-1 activity is regulated by SAX-3/ROBO acting on the RhoGAP HUM-7.

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Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis

Abstract: Adherens junction remodeling allows changes in cell shape and position. Zilberman et al. show through live imaging that CDC-42 is dispensable for epithelial cell polarization, but its RhoGAP-regulated activity is needed to control junctional actin organization during embryo elongation.

Cited by 42 publications

References 96 publications

A Polybasic Domain in aPKC Mediates Par6-Dependent Control of Membrane Targeting and Kinase Activity

A Polybasic Domain in aPKC Mediates Par6-Dependent Control of Membrane Targeting and Kinase Activity

Planar cell polarity in the C. elegans embryo emerges by differential retention of aPARs at cell-cell contacts

The RhoGAP HUM-7/Myo9 integrates signals to modulate RHO-1/RhoA during embryonic morphogenesis in Caenorhabditis elegans

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