Down-regulation of Stathmin Is Required for the Phenotypic Changes and Classical Activation of Macrophages

Xu, Kewei; Harrison, Rene E.

doi:10.1074/jbc.m115.639625

Cited by 16 publications

(9 citation statements)

References 93 publications

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“…Consistent with this idea, stabilizing MTs by Taxol treatment leads to the formation of membrane protrusions evenly distributed around the cell perimeter rather than mainly at the cell front ( Schiff and Horwitz, 1980 ; Waterman-Storer and Salmon, 1999 ). Down-regulation of the MT destabilizer, stathmin/Op18, also enhances membrane ruffles in macrophage activation ( Xu and Harrison, 2015 ), supporting the idea that global stabilization of MTs disrupts polarity. The enhanced formation of random protrusions and membrane ruffling upon the depletion of MCAK indicates that MCAK might be involved in regional suppression of signals to prevent the formation of extra protrusions around the periphery, thus ensuring a dominant lamellipodial protrusion for efficient migration.…”

Section: Discussionmentioning

confidence: 74%

Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration

Zong

Hazelbaker

Moe

et al. 2021

MBoC

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The asymmetric distribution of microtubule (MT) dynamics in migrating cells is important for cell polarization, yet the underlying regulatory mechanisms remain underexplored. Here, we addressed this question by studying the role of the MT depolymerase, MCAK, in the highly persistent migration of RPE-1 cells. MCAK knockdown leads to slowed migration and poor directional movement. Fixed and live cell imaging revealed that MCAK knockdown results in excessive membrane ruffling as well as defects in cell polarization and the maintenance of a major protrusive front. Additionally, loss of MCAK increases the lifetime of focal adhesions by decreasing their disassembly rate. These functions correlate with a spatial distribution of MCAK activity, wherein activity is higher in the trailing edge of cells compared to the leading edge. Overexpression of Rac1 has a dominant effect over MCAK activity, placing it downstream or in a parallel pathway to MCAK function in migration. Together, our data support a model in which the polarized distribution of MCAK activity and subsequent differential regulation of MT dynamics contribute to cell polarity, centrosome positioning and focal adhesion dynamics that all help facilitate robust directional migration. [Media: see text] [Media: see text]

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Section: Discussionmentioning

confidence: 74%

Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration

Zong

Hazelbaker

Moe

et al. 2021

MBoC

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“…Down-regulation of the MT destabilizer, Stathmin/Op18, also enhances membrane ruffles in macrophage activation (Xu and Harrison, 2015), supporting the idea that global stabilization of MTs disrupts polarity. The enhanced formation of random protrusions and membrane ruffling upon the depletion of MCAK indicates that MCAK might be involved in regional suppression of signals to prevent the formation of extra protrusions around the periphery, thus ensuring a dominant lamellipodial protrusion for efficient migration.…”

Section: Discussionmentioning

confidence: 58%

Spatial Regulation of MCAK Promotes Cell Polarization and Focal Adhesion Turnover to Drive Robust Cell Migration

Zong

Hazelbaker

Moe

et al. 2020

Preprint

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The asymmetric distribution of microtubule (MT) dynamics in migrating cells is important for cell polarization, yet the underlying regulatory mechanisms remain underexplored. Here, we addressed this question by studying the role of the MT depolymerase, MCAK, in the highly persistent migration of RPE-1 cells. MCAK knockdown leads to slowed migration and poor directional movement. Fixed and live cell imaging revealed that MCAK knockdown results in excessive membrane ruffling as well as defects in cell polarization and the maintenance of a major protrusive front. Additionally, loss of MCAK increases the lifetime of focal adhesions by decreasing their disassembly rate. These defects are due in part to the loss of the spatial distribution of MCAK activity, wherein activity is higher in the trailing edge of cells compared to the leading edge. Overexpression of Rac1 has a dominant effect over MCAK activity, placing it downstream or in a parallel pathway to MCAK function in migration. Together, our data support a model that places MCAK at a key nexus of a feedback loop, in which polarized distribution of MCAK activity and subsequent differential regulation of MT dynamics contributes to cell polarity and directional migration.

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“…STMN1 is a protein involved in cytoskeletal rearrangements that functions by binding to tubulin αβ heterodimers (microtubules), sequestering them and preventing microtubule assembly. The role of STMN1 on immune cells is contradictive, because its downregulation has been described as critical for microtubule stabilization and macrophage activation [ 60 ] and affects T cells polarization [ 61 ]. In our study, we found that over-expression of miR-221 and miR-210 could lead to downregulation of STMN1.…”

Section: Discussionmentioning

confidence: 99%

Regulatory role of microRNA in mesenteric lymph nodes after Salmonella Typhimurium infection

Herrera-Uribe

Zaldívar‐López

Aguilar

et al. 2018

Vet Res

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Salmonellosis is a gastrointestinal disease caused by non-typhoidal Salmonella serovars such as Salmonella Typhimurium. This pathology is a zoonosis, and food animals with subclinical infection constitute a vast reservoir for disease. After intestinal colonization, Salmonella Typhimurium reaches mesenteric lymph nodes (MLN), where infection is controlled avoiding systemic spread. Although the molecular basis of this infection has been extensively studied, little is known about how microRNA (miRNA) regulate the expression of proteins involved in the Salmonella-host interaction. Using small RNA-seq, we examined expression profiles of MLN 2 days after infection with Salmonella Typhimurium, and we found 110 dysregulated miRNA. Among them, we found upregulated miR-21, miR-155, miR-150, and miR-221, as well as downregulated miR-143 and miR-125, all of them previously linked to other bacterial infections. Integration with proteomic data revealed 30 miRNA potentially regulating the expression of 15 proteins involved in biological functions such as cell death and survival, inflammatory response and antigenic presentation. The inflammatory response was found increased via upregulation of miRNA such as miR-21 and miR-155. Downregulation of miR-125a/b, miR-148 and miR-1 were identified as potential regulators of MHC-class I components PSMB8, HSP90B1 and PDIA3, respectively. Furthermore, we confirmed that miR-125a is a direct target of immunoproteasome component PSMB8. Since we also found miR-130 downregulation, which is associated with upregulation of HSPA8, we suggest induction of both MHC-I and MHC-II antigen presentation pathways. In conclusion, our study identifies miRNA that could regulate critical networks for antigenic presentation, inflammatory response and cytoskeletal rearrangements.Electronic supplementary materialThe online version of this article (10.1186/s13567-018-0506-1) contains supplementary material, which is available to authorized users.

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Down-regulation of Stathmin Is Required for the Phenotypic Changes and Classical Activation of Macrophages

Cited by 16 publications

References 93 publications

Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration

Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration

Spatial Regulation of MCAK Promotes Cell Polarization and Focal Adhesion Turnover to Drive Robust Cell Migration

Regulatory role of microRNA in mesenteric lymph nodes after Salmonella Typhimurium infection

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