A particle size threshold governs diffusion and segregation of PAR-3 during cell polarization

Chang, Yiran; Dickinson, Daniel J.

doi:10.1016/j.celrep.2022.110652

Cited by 22 publications

(36 citation statements)

References 60 publications

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“…One curious observation is that PAR-3 segregation was largely unchanged as a function of oligomer size for all oligomers > 1, despite size-dependent changes in membrane association as evidenced by changes in the membrane:cytoplasmic ratio. On one level these results are somewhat consistent with recent suggestions of a size threshold for segregation (Chang and Dickinson, 2022). However, while prior work based on a nanobody-based clustering strategy suggested trimers as the minimal size required for segregation by cortical flows, in our experiments dimers and tetramers segregated with equal efficiency, suggesting that the dominant criteria is not oligomer size, but whether PAR-3 is oligomerized or not.…”

Section: Discussionsupporting

confidence: 92%

“…Division asymmetry, cortical flow rates, embryonic lethality, and adult sterility appeared normal in both 2mer and 4mer variants (Figure S1). Thus, our data show that ectopic oligomerization of monomeric PAR-3 mutants rescues PAR-3 function, and in contrast to prior results (Chang and Dickinson, 2022), dimerization appears to be sufficient.…”

Section: Rescue Of Cluster-defective Par-3contrasting

confidence: 91%

“…In such a model clustering would effectively tune the physical coupling of molecules to the actomyosin cortex, allowing molecules to selectively 'sense flows.' Consistent with such a model, PAR-3 diffusive mobility is restricted by the actin cortex in embryos (Sailer et al, 2015) and recent work has suggested a strict size threshold for directional transport by cortical flows (Chang and Dickinson, 2022). At the same time, clustering of molecules could also serve to reduce diffusivity and enhance membrane association via avidity effects, both of which would also be expected to enhance the efficiency of transport by cortical flow.…”

Section: Introductionmentioning

confidence: 69%

“…Whether this universal coupling of PAR proteins to cortical actin flows points towards a paradigm of bulk membrane flow remains unclear. None of the PAR proteins show obvious colocalization with actin and do not require actin to stabilize their localization to the membrane (Chang and Dickinson, 2022; Goehring et al, 2011a; Munro et al, 2004). However, lateral mobility of PAR-3 is enhanced by depolymerization of actin (Sailer et al, 2015) and it is possible that PAR proteins may nonetheless be molecularly linked to the actin cortex, perhaps through association into higher order, heterogenous assemblies with other proteins or lipids at the membrane:cortex interface.…”

Section: Discussionmentioning

confidence: 99%

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Design principles for selective polarization of PAR proteins by cortical flows

Illukkumbura

Hirani

Borrego-Pinto

et al. 2022

Preprint

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Clustering of membrane-associated molecules has long been proposed to promote size-dependent interactions with the actomyosin cortical network, thereby allowing them to be transported by actin flow. Consistent with such a model, clustering of the conserved polarity protein PAR-3 in the C. elegans zygote is essential for its polarization by cortical actomyosin flows, and clusters of PAR-3 visibly move with flows. However, here we show that advection by cortical flow is independent of clustering. Clustered and non-clustered PAR-3 variants are advected equally well over short timescales by cortical actin flow as are other PAR proteins. Moreover, we see no strong links between advection and either cluster size or diffusivity that would be consistent with size-dependent interactions with the actin cortex. Instead, using a combination of experiment and theory, we find that efficient long range transport of PAR proteins by cortical flow is primarily tuned by the stability of membrane association, which is enhanced by clustering and determines the persistence of both transport by flow and the resulting asymmetries once flows cease. Consistent with this model, stabilizing membrane association was sufficient to induce segregation of a non-segregating PAR protein, effectively inverting its polarity. We conclude that the impact of advection on membrane-associated proteins is much broader than previously anticipated and thus cells must appropriately tune membrane association dynamics to achieve selectivity in the long range transport of membrane-associated molecules by cortical flows.

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Section: Discussionsupporting

confidence: 92%

Section: Rescue Of Cluster-defective Par-3contrasting

confidence: 91%

Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Design principles for selective polarization of PAR proteins by cortical flows

Illukkumbura

Hirani

Borrego-Pinto

et al. 2022

Preprint

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“…Indeed, HMP-1 gut(-) foci still localized HMR-1, PAR-3, and PKC-3. Some minimal degree of clustering may be required for the transport of these proteins, as also observed in the C. elegans zygote (Chang and Dickinson, 2022), but perhaps further abrogating clustering is needed to uncover such defects. For example, the p120 catenin homolog JAC-1, which was not tested here, could act on its own or in parallel to HMP-1 and HMP-2 to further promote clustering and polarization.…”

Section: Discussionmentioning

confidence: 96%

E-cadherin/HMR-1 and PAR-3 break symmetry at stable cell contacts in a developing epithelium

Naturale

Pickett

Feldman

2022

Preprint

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SummaryTissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. Using the C. elegans intestinal epithelium, we identified a patterning mechanism informed by stabilized cell/cell contact and executed via the scaffolding protein PAR-3 and the transmembrane protein E-cadherin/HMR-1. Intestinal cells break symmetry as PAR-3 and HMR-1 recruit apical determinants into micron-scale ‘local polarity complexes’ (LPCs) at homotypic contacts. LPCs undergo a HMR-1-based migration to a common tissue midline, thereby establishing tissue-wide polarity. Thus, symmetry breaking results from PAR-3-dependent intracellular polarization coupled to HMR-1-based tissue-level communication that occurs through a non-adhesive signaling role for HMR-1. Intestinal cells gain initial asymmetry from differential contact duration as homotypic contacts last longer than heterotypic contacts, thus providing stable platforms for LPC assembly and offering a logical and likely conserved framework for how internal epithelia with no obvious pre-existing asymmetries can polarize.

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