scholarly journals Chaperone-Assisted Mitotic Actin Remodeling by BAG3 and HSPB8 Involves the Deacetylase HDAC6 and Its Substrate Cortactin

2020 ◽  
Vol 22 (1) ◽  
pp. 142
Author(s):  
Carole Luthold ◽  
Alice-Anaïs Varlet ◽  
Herman Lambert ◽  
François Bordeleau ◽  
Josée N. Lavoie
Keyword(s):  
Molecular Mechanisms ◽  
Protein Quality ◽  
Spatial Dynamics ◽  
Mitotic Cell ◽  
Actin Dynamics ◽  
Spindle Orientation ◽  
Actin Remodeling ◽  
Spindle Positioning ◽  
Cell Rounding

The fidelity of actin dynamics relies on protein quality control, but the underlying molecular mechanisms are poorly defined. During mitosis, the cochaperone BCL2-associated athanogene 3 (BAG3) modulates cell rounding, cortex stability, spindle orientation, and chromosome segregation. Mitotic BAG3 shows enhanced interactions with its preferred chaperone partner HSPB8, the autophagic adaptor p62/SQSTM1, and HDAC6, a deacetylase with cytoskeletal substrates. Here, we show that depletion of BAG3, HSPB8, or p62/SQSTM1 can recapitulate the same inhibition of mitotic cell rounding. Moreover, depletion of either of these proteins also interfered with the dynamic of the subcortical actin cloud that contributes to spindle positioning. These phenotypes were corrected by drugs that limit the Arp2/3 complex or HDAC6 activity, arguing for a role for BAG3 in tuning branched actin network assembly. Mechanistically, we found that cortactin acetylation/deacetylation is mitotically regulated and is correlated with a reduced association of cortactin with HDAC6 in situ. Remarkably, BAG3 depletion hindered the mitotic decrease in cortactin–HDAC6 association. Furthermore, expression of an acetyl-mimic cortactin mutant in BAG3-depleted cells normalized mitotic cell rounding and the subcortical actin cloud organization. Together, these results reinforce a BAG3′s function for accurate mitotic actin remodeling, via tuning cortactin and HDAC6 spatial dynamics.

scholarly journals Rnd3 interacts with TAO kinases and contributes to mitotic cell rounding and spindle positioning

2020 ◽  
Vol 133 (6) ◽  
pp. jcs235895
Author(s):  
Ritu Garg ◽  
Chuay-Yeng Koo ◽  
Elvira Infante ◽  
Caterina Giacomini ◽  
Anne J. Ridley ◽  
...  
Keyword(s):  
Mitotic Cell ◽  
Spindle Positioning ◽  
Cell Rounding

scholarly journals Phosphorylation of an Arabidopsis villin activates host actin remodeling to restrict microbial invasion

2021 ◽  
Author(s):  
Minxia Zou ◽  
Mengmeng Guo ◽  
Zhaoyang Zhou ◽  
Bingxiao Xiao ◽  
Qing Pan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Molecular Mechanisms ◽  
Actin Dynamics ◽  
Actin Remodeling ◽  
Dynamic Framework ◽  
Host Cytoplasm ◽  
Microbial Invasion ◽  
Mitogen Activated Protein

Abstract Actin cytoskeleton is a dynamic framework of cytoplasmic filaments that rearranges as the needs of the cell change during growth and development. Incessant turnover mechanisms allow these networks to be rapidly redeployed in defense of host cytoplasm against microbial invaders. However, the precise functions of host actin and the molecular mechanisms underlying actin rearrangements in host defense remain largely unknown. Here, we uncover the mechanism by which host actin controls innate immunity gates on plant surface to actively prevent microbial entry into internal tissue. VLN3, a villin protein from Arabidopsis is a key regulator of this process. Our in vitro and in vivo phosphorylation assays show that VLN3 is a physiological substrate of two pathogen-responsive mitogen-activated protein kinases (MAPKs). Quantitative analyses of actin dynamics and genetic studies reveal that phosphorylation of VLN3 by MAPKs govern actin remodeling to activate innate immunity gating on host surface.

scholarly journals Prostate-derived Sterile 20-like Kinases (PSKs/TAOKs) Are Activated in Mitosis and Contribute to Mitotic Cell Rounding and Spindle Positioning

2011 ◽  
Vol 286 (34) ◽  
pp. 30161-30170 ◽  
Author(s):  
Rachael L. Wojtala ◽  
Ignatius A. Tavares ◽  
Penny E. Morton ◽  
Ferran Valderrama ◽  
N. Shaun B. Thomas ◽  
...  
Keyword(s):  
Mitotic Cell ◽  
Spindle Positioning ◽  
Cell Rounding

scholarly journals Inversin modulates the cortical actin network during mitosis

2013 ◽  
Vol 305 (1) ◽  
pp. C36-C47 ◽  
Author(s):  
Michael E. Werner ◽  
Heather H. Ward ◽  
Carrie L. Phillips ◽  
Caroline Miller ◽  
Vincent H. Gattone ◽  
...  
Keyword(s):  
Cell Division ◽  
Mammalian Cells ◽  
Cyst Formation ◽  
Mitotic Cell ◽  
Mouse Embryos ◽  
Cortical Actin ◽  
Division Plane ◽  
Spindle Positioning ◽  
Actin Organization ◽  
Cell Rounding

Mutations in inversin cause nephronophthisis type II, an autosomal recessive form of polycystic kidney disease associated with situs inversus, dilatation, and kidney cyst formation. Since cyst formation may represent a planar polarity defect, we investigated whether inversin plays a role in cell division. In developing nephrons from inv−/− mouse embryos we observed heterogeneity of nuclear size, increased cell membrane perimeters, cells with double cilia, and increased frequency of binuclear cells. Depletion of inversin by siRNA in cultured mammalian cells leads to an increase in bi- or multinucleated cells. While spindle assembly, contractile ring formation, or furrow ingression appears normal in the absence of inversin, mitotic cell rounding and the underlying rearrangement of the cortical actin cytoskeleton are perturbed. We find that inversin loss causes extensive filopodia formation in both interphase and mitotic cells. These cells also fail to round up in metaphase. The resultant spindle positioning defects lead to asymmetric division plane formation and cell division. In a cell motility assay, fibroblasts isolated from inv−/− mouse embryos migrate at half the speed of wild-type fibroblasts. Together these data suggest that inversin is a regulator of cortical actin required for cell rounding and spindle positioning during mitosis. Furthermore, cell division defects resulting from improper spindle position and perturbed actin organization contribute to altered nephron morphogenesis in the absence of inversin.

scholarly journals RhoA is required for cortical retraction and rigidity during mitotic cell rounding

2003 ◽  
Vol 160 (2) ◽  
pp. 255-265 ◽  
Author(s):  
Amy Shaub Maddox ◽  
Keith Burridge
Keyword(s):  
Actin Cytoskeleton ◽  
Molecular Mechanisms ◽  
Shape Change ◽  
Rho Kinase ◽  
Mitotic Cell ◽  
Cortical Actin ◽  
Interphase Cell ◽  
Cell Rounding ◽  
Rhoa Activity ◽  
Cell Shape Change

Mitotic cell rounding is the process of cell shape change in which a flat interphase cell becomes spherical at the onset of mitosis. Rearrangement of the actin cytoskeleton, de-adhesion, and an increase in cortical rigidity accompany mitotic cell rounding. The molecular mechanisms that contribute to this process have not been defined. We show that RhoA is required for cortical retraction but not de-adhesion during mitotic cell rounding. The mitotic increase in cortical rigidity also requires RhoA, suggesting that increases in cortical rigidity and cortical retraction are linked processes. Rho-kinase is also required for mitotic cortical retraction and rigidity, indicating that the effects of RhoA on cell rounding are mediated through this effector. Consistent with a role for RhoA during mitotic entry, RhoA activity is elevated in rounded, preanaphase mitotic cells. The activity of the RhoA inhibitor p190RhoGAP is decreased due to its serine/threonine phosphorylation at this time. Cumulatively, these results suggest that the mitotic increase in RhoA activity leads to rearrangements of the cortical actin cytoskeleton that promote cortical rigidity, resulting in mitotic cell rounding.

scholarly journals Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair

PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009186
Author(s):  
Mitsutoshi Nakamura ◽  
Jeffrey M. Verboon ◽  
Tessa E. Allen ◽  
Maria Teresa Abreu-Blanco ◽  
Raymond Liu ◽  
...  
Keyword(s):  
Wound Repair ◽  
Molecular Mechanisms ◽  
Actin Dynamics ◽  
Cell Cortex ◽  
Healthy Individuals ◽  
Actin Remodeling ◽  
Ring Assembly ◽  
Drug Inhibition ◽  
Inhibition Studies ◽  
Cortical Cytoskeleton

Cells are exposed to frequent mechanical and/or chemical stressors that can compromise the integrity of the plasma membrane and underlying cortical cytoskeleton. The molecular mechanisms driving the immediate repair response launched to restore the cell cortex and circumvent cell death are largely unknown. Using microarrays and drug-inhibition studies to assess gene expression, we find that initiation of cell wound repair in the Drosophila model is dependent on translation, whereas transcription is required for subsequent steps. We identified 253 genes whose expression is up-regulated (80) or down-regulated (173) in response to laser wounding. A subset of these genes were validated using RNAi knockdowns and exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that the canonical insulin signaling pathway controls actin dynamics through the actin regulators Girdin and Chickadee (profilin), and its disruption leads to abnormal wound repair. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.

scholarly journals Autocrine insulin pathway signaling regulates actin dynamics in cell wound repair

2020 ◽  
Author(s):  
Mitsutoshi Nakamura ◽  
Jeffrey M. Verboon ◽  
Tessa E. Allen ◽  
Maria Teresa Abreu-Blanco ◽  
Raymond Liu ◽  
...  
Keyword(s):  
Wound Repair ◽  
Molecular Mechanisms ◽  
Actin Dynamics ◽  
Cell Cortex ◽  
Healthy Individuals ◽  
Actin Remodeling ◽  
Ring Assembly ◽  
Drug Inhibition ◽  
Inhibition Studies ◽  
Cortical Cytoskeleton

AbstractCells are exposed to frequent mechanical and/or chemical stressors that can compromise the integrity of the plasma membrane and underlying cortical cytoskeleton. The molecular mechanisms driving the immediate repair response launched to restore the cell cortex and circumvent cell death are largely unknown. Using microarrays and drug-inhibition studies to assess gene expression, we find that initiation of cell wound repair in the Drosophila model is dependent on translation, whereas transcription is required for subsequent steps. We identified 253 genes whose expression is up-regulated (80) or down-regulated (173) in response to laser wounding. A subset of these genes were validated using RNAi knockdowns and exhibit aberrant actomyosin ring assembly and/or actin remodeling defects. Strikingly, we find that the canonical insulin signaling pathway controls actin dynamics through the actin regulators Girdin and Chickadee (profilin), and its disruption leads to abnormal wound repair. Our results provide new insight for understanding how cell wound repair proceeds in healthy individuals and those with diseases involving wound healing deficiencies.

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