Self-organization of protrusions and polarity during eukaryotic chemotaxis

Graziano, Brian R.; Weiner, Orion D.

doi:10.1016/j.ceb.2014.06.007

Cited by 69 publications

(82 citation statements)

References 87 publications

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“…In terms of molecular mechanisms, eukaryotic chemotaxis requires actin remodeling via actin-associated proteins to form actin aggregates or clusters, followed by short protrusions, in a process very similar to neuritogenesis [66][67][68]. Why then do non-neuronal cells not extend neurites?…”

Section: Discussionmentioning

confidence: 99%

Actin Aggregations Mark the Sites of Neurite Initiation

et al. 2016

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A salient feature of neurons is their intrinsic ability to grow and extend neurites, even in the absence of external cues. Compared to the later stages of neuronal development, such as neuronal polarization and dendrite morphogenesis, the early steps of neuritogenesis remain relatively unexplored. Here we showed that redistribution of cortical actin into large aggregates preceded neuritogenesis and determined the site of neurite initiation. Enhancing actin polymerization by jasplakinolide treatment effectively blocked actin redistribution and neurite initiation, while treatment with the actin depolymerizing agents latrunculin A or cytochalasin D accelerated neurite formation. Together, these results demonstrate a critical role of actin dynamics and reorganization in neurite initiation. Further experiments showed that microtubule dynamics and protein synthesis are not required for neurite initiation, but are required for later neurite stabilization. The redistribution of actin during early neuronal development was also observed in the cerebral cortex and hippocampus in vivo.

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Section: Discussionmentioning

confidence: 99%

Actin Aggregations Mark the Sites of Neurite Initiation

et al. 2016

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“…Circulating naive neutrophils are apolar, but upon stimulation by chemoattractants they rapidly polarize in a manner that is epitomized by formation of lamellar-type F actin at the front and localization of active RHOA and phosphorylated myosin light chain (pMLC, also known as MYL2) at the back (Bourne and Weiner, 2002;Graziano and Weiner, 2014;Liu and Parent, 2011;Wang, 2009;Wu, 2005). It remains, however, incompletely understood how RHOA activation and pMLC localization is polarized.…”

Section: Introductionmentioning

confidence: 99%

Front Signal-Dependent Accumulation of RHOA Inhibitor FAM65B at Leading Edges Polarizes Neutrophils

Gao

Tang

et al. 2015

Journal of Cell Science

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A hallmark of neutrophil polarization is the back localization of active RHOA and phosphorylated myosin light chain (pMLC, also known as MYL2). However, the mechanism for the polarization is not entirely clear. Here, we show that FAM65B, a newly identified RHOA inhibitor, is important for the polarization. When FAM65B is phosphorylated, it binds to 14-3-3 family proteins and becomes more stable. In neutrophils, chemoattractants stimulate FAM65B phosphorylation largely depending on the signals from the front of the cells that include those mediated by phospholipase Cb (PLCb) and phosphoinositide 3-kinase c (PI3Kc), leading to FAM65B accumulation at the leading edge. Concordantly, FAM65B deficiency in neutrophils resulted in an increase in RHOA activity and localization of pMLC to the front of cells, as well as defects in chemotaxis directionality and adhesion to endothelial cells under flow. These data together elucidate a mechanism for RHOA and pMLC polarization in stimulated neutrophils through direct inhibition of RHOA by FAM65B at the leading edge.

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“…Propagating wave-like patterns of actin polymerization have been observed in migrating cells (e.g., neutrophils), which play a role in regulating motility and chemotaxis through the formation of protrusions (21,22). Another example was recently identified at the adhesive junctions between simple polarized epithelial cells (23).…”

Section: Introductionmentioning

confidence: 99%

Self-Organizing Actomyosin Patterns on the Cell Cortex at Epithelial Cell-Cell Junctions

Moore

Michael

et al. 2014

Biophysical Journal

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The behavior of actomyosin critically determines morphologically distinct patterns of contractility found at the interface between adherent cells. One such pattern is found at the apical region (zonula adherens) of cell-cell junctions in epithelia, where clusters of the adhesion molecule E-cadherin concentrate in a static pattern. Meanwhile, E-cadherin clusters throughout lateral cell-cell contacts display dynamic movements in the plane of the junctions. To gain insight into the principles that determine the nature and organization of these dynamic structures, we analyze this behavior by modeling the 2D actomyosin cell cortex as an active fluid medium. The numerical simulations show that the stability of the actin filaments influences the spatial structure and dynamics of the system. We find that in addition to static Turing-type patterns, persistent dynamic behavior occurs in a wide range of parameters. In the 2D model, mechanical stress-dependent actin breakdown is shown to produce a continuously changing network of actin bridges, whereas with a constant breakdown rate, more isolated clusters of actomyosin tend to form. The model qualitatively reproduces the dynamic and stable patterns experimentally observed at the junctions between epithelial cells.

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Self-organization of protrusions and polarity during eukaryotic chemotaxis

Cited by 69 publications

References 87 publications

Actin Aggregations Mark the Sites of Neurite Initiation

Actin Aggregations Mark the Sites of Neurite Initiation

Front Signal-Dependent Accumulation of RHOA Inhibitor FAM65B at Leading Edges Polarizes Neutrophils

Self-Organizing Actomyosin Patterns on the Cell Cortex at Epithelial Cell-Cell Junctions

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