Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs

Bailey, Matthew; Prehoda, Kenneth E.

doi:10.1016/j.devcel.2015.09.016

Cited by 95 publications

(136 citation statements)

References 77 publications

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“…Consistently, a previous study demonstrated that the electrostatic-based interaction of N-WASP with PI(4,5)P2 is multivalent, and that this contributes both to the cooperativity of this protein-lipid interaction and to the ultrasensitive, switch-like kinetics of actin polymerization (Papayannopoulos et al, 2005). Multivalent protein-lipid interactions also underlie Par polarity complex localization to anionic lipids at the cortex, where basic-hydrophobic domains resemble the BC motifs that we identify in Bem1 (Bailey & Prehoda, 2015). Multivalent protein-lipid interactions also underlie Par polarity complex localization to anionic lipids at the cortex, where basic-hydrophobic domains resemble the BC motifs that we identify in Bem1 (Bailey & Prehoda, 2015).…”

Section: Of 19supporting

confidence: 90%

“…Since polarity establishment is also a switch-like process, it is conceivable that cooperativity in the Bem1-lipid interaction may contribute to these properties. Multivalent protein-lipid interactions also underlie Par polarity complex localization to anionic lipids at the cortex, where basic-hydrophobic domains resemble the BC motifs that we identify in Bem1 (Bailey & Prehoda, 2015). Similarly, multivalent protein-lipid interactions play a role in the recruitment of dynamin, EEA1, retromer, and ESCRT-III complexes to membranes (Lemmon & Ferguson, 2000;Seaman & Williams, 2002;Hayakawa et al, 2004;Buchkovich et al, 2013).…”

Section: Discussionsupporting

confidence: 55%

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Avidity‐driven polarity establishment via multivalent lipid– GTP ase module interactions

et al. 2018

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While Rho GTPases are indispensible regulators of cellular polarity, the mechanisms underlying their anisotropic activation at membranes have been elusive. Using the budding yeast Cdc42 GTPase module, which includes a guanine nucleotide exchange factor (GEF) Cdc24 and the scaffold Bem1, we find that avidity generated via multivalent anionic lipid interactions is a critical mechanistic constituent of polarity establishment. We identify basic cluster (BC) motifs in Bem1 that drive the interaction of the scaffold-GEF complex with anionic lipids at the cell pole. This interaction appears to influence lipid acyl chain ordering, thus regulating membrane rigidity and feedback between Cdc42 and the membrane environment. Sequential mutation of the Bem1 BC motifs, PX domain, and the PH domain of Cdc24 lead to a progressive loss of cellular polarity stemming from defective Cdc42 nanoclustering on the plasma membrane and perturbed signaling. Our work demonstrates the importance of avidity via multivalent anionic lipid interactions in the spatial control of GTPase activation.

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Section: Of 19supporting

confidence: 90%

Section: Discussionsupporting

confidence: 55%

Avidity‐driven polarity establishment via multivalent lipid– GTP ase module interactions

et al. 2018

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“…One breakthrough in recent studies is the identification of so-called polybasic (i.e. basichydrophobic) domains in several polarity proteins such as Lgl, Numb and Miranda (Bailey and Prehoda, 2015;Dong et al, 2015). Polybasic domains are short but highly positively charged due to the enrichment of basic Arg/Lys residues.…”

Section: Introductionmentioning

confidence: 99%

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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“…7A). Recently, studies on a biochemically diverse group of proteins from different organisms demonstrated that protein domains required for membrane association could be reliably predicted based on their basic and hydrophobic score (BH score) above a critical threshold value of 0.6 (Bailey and Prehoda, 2015;Brzeska et al, 2010). Accordingly, the biophysical properties, determined by, for example, the BH score rather than amino acid conservation, could control protein-membrane associations.…”

Section: D6pk Plasma Membrane Association Is Phospholipid Dependentmentioning

confidence: 99%

Phospholipid composition and a polybasic motif determine D6 PROTEIN KINASE polar association with the plasma membrane and tropic responses

et al. 2016

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Polar transport of the phytohormone auxin through PIN-FORMED (PIN) auxin efflux carriers is essential for the spatiotemporal control of plant development. The Arabidopsis thaliana serine/threonine kinase D6 PROTEIN KINASE (D6PK) is polarly localized at the plasma membrane of many cells where it colocalizes with PINs and activates PIN-mediated auxin efflux. Here, we show that the association of D6PK with the basal plasma membrane and PINs is dependent on the phospholipid composition of the plasma membrane as well as on the phosphatidylinositol phosphate 5-kinases PIP5K1 and PIP5K2 in epidermis cells of the primary root. We further show that D6PK directly binds polyacidic phospholipids through a polybasic lysine-rich motif in the middle domain of the kinase. The lysine-rich motif is required for proper PIN3 phosphorylation and for auxin transport-dependent tropic growth. Polybasic motifs are also present at a conserved position in other D6PK-related kinases and required for membrane and phospholipid binding. Thus, phospholipid-dependent recruitment to membranes through polybasic motifs might not only be required for D6PK-mediated auxin transport but also other processes regulated by these, as yet, functionally uncharacterized kinases.

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Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs

Cited by 95 publications

References 77 publications

Avidity‐driven polarity establishment via multivalent lipid– GTP ase module interactions

Avidity‐driven polarity establishment via multivalent lipid– GTP ase module interactions

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

Phospholipid composition and a polybasic motif determine D6 PROTEIN KINASE polar association with the plasma membrane and tropic responses

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