Elaborating polarity: PAR proteins and the cytoskeleton

Nance, Jeremy; Zallen, Jennifer A.

doi:10.1242/dev.053538

Cited by 148 publications

(163 citation statements)

References 147 publications

(223 reference statements)

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“…These properties are dependent on proper cell polarization. Cell polarization relies on the ability of the cytoskeleton to establish unique domains at the cell cortex that govern the local function and activity of specific proteins (Drubin and Nelson, 1996;Nance and Zallen, 2011). The Rho family of small GTPases serves as the primary regulator of the actin cytoskeleton, and thereby cell polarity and movement (Ridley, 2006).…”

Section: Introductionmentioning

confidence: 99%

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

Hercyk

Rich

Das

2018

Preprint

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Cdc42, a conserved regulator of cell polarity, is activated by two GEFs, Gef1 and Scd1, in fission yeast. While gef1 and scd1 mutants exhibit distinct phenotypes, how they do so is unclear given that they activate the same GTPase. Using the GEF localization pattern during cytokinesis as a paradigm, we report a novel interplay between Gef1 and Scd1 that spatially modulates Cdc42. We find that Gef1 promotes Scd1 localization to the division site during cytokinesis and to the new end during polarized growth through the recruitment of the scaffold Scd2 via a Cdc42 feedforward pathway. Gef1-mediated Scd1 recruitment at the new end enables the transition from monopolar to bipolar growth. Reciprocally, Scd1 restricts Gef1 localization to prevent ectopic Cdc42 activation during cytokinesis to promote cell separation and during interphase to maintain cell shape. Our findings reveal an elegant regulatory pattern in which Gef1 establishes new sites of Scd1-mediated Cdc42 activity, while Scd1 restricts Gef1 to functional sites. We propose that crosstalk between GEFs is a conserved mechanism that orchestrates Cdc42 activation during complex cellular processes.Summary StatementCdc42 GEFs Gef1 and Scd1 crosstalk to fine-tune Cdc42 activity. This crosstalk promotes bipolar growth and maintains cell shape in fission yeast.

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Section: Introductionmentioning

confidence: 99%

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

Hercyk

Rich

Das

2018

Preprint

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“…Many cell polarities are orchestrated by the partitioning-defective (Par) 2 complex, which consists of Bazooka (Baz; aka Par-3), Par-6, and atypical protein kinase C (aPKC) (1)(2)(3). Although the Par complex plays a central role in polarizing many cell types, ectopic activity, particularly of aPKC, can lead to loss of polarity with severe consequences such as tissue disorganization and tumorigenesis (4 -6), suggesting that Par complex output must be precisely controlled.…”

mentioning

confidence: 99%

Partitioning-defective Protein 6 (Par-6) Activates Atypical Protein Kinase C (aPKC) by Pseudosubstrate Displacement

Graybill

Wee

Atwood

et al. 2012

Journal of Biological Chemistry

117

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The phosphorylation activity of atypical Protein Kinase C (aPKC) is central to the establishment of cell polarity by Par complex. Like other PKC family members, aPKC contains a pseudosubstrate domain that binds to the active site in the kinase domain and acts as an internal inhibitor. Despite the presence of the cis‐acting inhibitor, another Par complex member, Par‐6, is thought to repress aPKC activity. To examine the precise mechanism by which the pseudosubstrate domain and Par‐6 regulate aPKC activity, we reconstitute the system in vitro and performed a detailed kinetic analysis. We confirm that the pseudosubstrate domain is responsible for the autoinhibition. Surprisingly, rather than acting as an inhibitor, Par‐6 activates aPKC by displacing the pseudosubstrate from the kinase domain. Par‐6 activation of aPKC is consistent with our observation that Par‐6/aPKC complex, but not aPKC alone, is competent to release its substrate from the cell membrane in Drosophila S2 cells. Our data support a model in which Par‐6 displacement of aPKC pseudosubstrate domain is required for the diverse cell polarities mediated by the Par complex. NIH Grant 068032

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“…group of PAR (partition defective) proteins establish epithelial cell polarity and bilateral symmetry (Goldstein and Macara, 2007;Nance and Zallen, 2011). In mammals, three major polarity complexes regulate the apical and basolateral polarity of epithelial cells, the PAR (CDC42-PAR3-PAR6-aPKC), Crumb (Crb-PALS-PATJ) and Scribble (Scrib-Dlg-Lgl) complexes.…”

Section: Polar Protein Trafficking In Prokaryotes and Eukaryotesmentioning

confidence: 99%

“…In bacterial and mammalian systems, several proteins interacting with those 'polar' proteins have been identified (Nance and Zallen, 2011;Tsokos et al, 2010 …”

Section: Polar Protein Trafficking In Prokaryotes and Eukaryotesmentioning

confidence: 99%

Regulation of the Polarity of Protein Trafficking by Phosphorylation

Ganguly

Sasayama

Cho

2012

Molecules and Cells

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The asymmetry of environmental stimuli and the execution of developmental programs at the organism level require a corresponding polarity at the cellular level, in both unicellular and multicellular organisms. In plants, cell polarity is important in major developmental processes such as cell division, cell enlargement, cell morphogenesis, embryogenesis, axis formation, organ development, and defense. One of the most important factors controlling cell polarity is the asymmetric distribution of polarity determinants. In particular, phosphorylation is implicated in the polar distribution of the determinant protein factors, a mechanism conserved in both prokaryotes and eukaryotes. In plants, formation of local gradients of auxin, the morphogenic hormone, is critical for plant developmental processes exhibiting polarity. The auxin efflux carriers PIN-FORMEDs (PINs) localize asymmetrically in the plasma membrane and cause the formation of local auxin gradients throughout the plant. The asymmetry of PIN distribution in the plasma membrane is determined by phosphorylationmediated polar trafficking of PIN proteins. This review discusses recent studies on the role of phosphorylation in polar PIN trafficking.

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Elaborating polarity: PAR proteins and the cytoskeleton

Cited by 148 publications

References 147 publications

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

Partitioning-defective Protein 6 (Par-6) Activates Atypical Protein Kinase C (aPKC) by Pseudosubstrate Displacement

Regulation of the Polarity of Protein Trafficking by Phosphorylation

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