Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge

Ruiz-Sáenz, Ana; Kremer, Leonor; Alonso, Miguel A.; Millán, Jaime; Correas, Isabel

doi:10.1242/jcs.083634

Cited by 32 publications

(41 citation statements)

References 42 publications

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“…3B). As described before, ECV304 cells contain several 4.1R isoforms (Ruiz-Sáenz et al, 2011), which are mainly produced by alternative splicing (Conboy, 1999;Tang et al, 1990). Although several 4.1R isoforms were found in the cell extract, only the ,80-kDa 4.1R species was detected in the GFP-CLASP2 immunoprecipitates (Fig.…”

Section: Protein 41r Interacts With Clasp2supporting

confidence: 62%

“…In addition, a role for 4.1R as a linker between the actin cytoskeleton and components of tight junctions (Mattagajasingh et al, 2000) and adherens junctions (Yang et al, 2009) has been reported. Recently, we showed that 4.1R selectively accumulates at the leading edge of migrating cells and that its depletion affects cell motility (Ruiz-Sáenz et al, 2011). All these findings indicate that 4.1R is not only an adaptor protein linking transmembrane proteins and the actin cytoskeleton but also a multifunctional protein acting at different subcellular sites.…”

Section: Introductionmentioning

confidence: 88%

“…1A), either used individually (siRNA1, siRNA2) or as a pool (siRNA_pool, or si4.1R). The same siRNAs were previously employed to characterize the role of 4.1R in cell migration (Ruiz-Sáenz et al, 2011). Immunofluorescence analysis of control migratory cells showed that MTs formed a dense radial array oriented roughly perpendicular to the cell edge (Fig.…”

Section: Protein 41r Is Involved In Mt Organizationmentioning

confidence: 98%

“…We have recently shown that protein 4.1R selectively accumulates at the leading edge and is necessary for cell migration (Ruiz-Sáenz et al, 2011). It is therefore plausible that 4.1R has a role in MT organization at the cell edge.…”

Section: Protein 41r Is Involved In Mt Organizationmentioning

confidence: 99%

“…One possible explanation for this is that 4.1R proteins can adopt different conformations (Pérez-Ferreiro et al, 2006) and that, in the case of 4.1R 60 , a region that is important for the interaction may be hindered. The CORE region of 4.1R is also involved in binding to the scaffolding protein IQGAP1 (Ruiz-Sáenz et al, 2011), which is also a CLASP2-binding partner (Watanabe et al, 2009). Because the 4.1R-CLASP2 association can occur in IQGAP1-KD cells (supplementary material Fig.…”

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confidence: 99%

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Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex

Ruiz-Sáenz¹,

Haren²,

Sayas³

et al. 2013

Journal of Cell Science

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SummaryThe microtubule (MT) cytoskeleton is essential for many cellular processes, including cell polarity and migration. Cortical platforms, formed by a subset of MT plus-end-tracking proteins, such as CLASP2, and non-MT binding proteins such as LL5b, attach distal ends of MTs to the cell cortex. However, the mechanisms involved in organizing these platforms have not yet been described in detail. Here we show that 4.1R, a FERM-domain-containing protein, interacts and colocalizes with cortical CLASP2 and is required for the correct number and dynamics of CLASP2 cortical platforms. Protein 4.1R also controls binding of CLASP2 to MTs at the cell edge by locally altering GSK3 activity. Furthermore, in 4.1R-knockdown cells MT plus-ends were maintained for longer in the vicinity of cell edges, but instead of being tethered to the cell cortex, MTs continued to grow, bending at cell margins and losing their radial distribution. Our results suggest a previously unidentified role for the scaffolding protein 4.1R in locally controlling CLASP2 behavior, CLASP2 cortical platform turnover and GSK3 activity, enabling correct MT organization and dynamics essential for cell polarity.

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Section: Protein 41r Interacts With Clasp2supporting

confidence: 62%

Section: Introductionmentioning

confidence: 88%

Section: Protein 41r Is Involved In Mt Organizationmentioning

confidence: 98%

Section: Protein 41r Is Involved In Mt Organizationmentioning

confidence: 99%

mentioning

confidence: 99%

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Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex

Ruiz-Sáenz¹,

Haren²,

Sayas³

et al. 2013

Journal of Cell Science

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EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis

Bañón-Rodríguez

Gálvez-Santisteban

Vergarajaúregui

et al. 2014

EMBO J

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Establishing the correct orientation of the mitotic spindle is an essential step in epithelial cell division in order to ensure that epithelial tubules form correctly during organ development and regeneration. While recent findings have identified some of the molecular mechanisms that underlie spindle orientation, many aspects of this process remain poorly understood. Here, we have used the 3D-MDCK model system to demonstrate a key role for a newly identified protein complex formed by IQGAP1 and the epithelial growth factor receptor (EGFR) in controlling the orientation of the mitotic spindle. IQGAP1 is a scaffolding protein that regulates many cellular pathways, from cell-cell adhesion to microtubule organization, and its localization in the basolateral membrane ensures correct spindle orientation. Through its IQ motifs, IQGAP1 binds to EGFR, which is responsible for maintaining IQGAP1 in the basolateral membrane domain. Silencing IQGAP1, or disrupting the basolateral localization of either IQGAP1 or EGFR, results in a non-polarized distribution of NuMA, mitotic spindle misorientation and defects in single lumen formation.

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Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells

Cacho-Navas

Reglero-Real

Colás-Algora

et al. 2022

Cell. Mol. Life Sci.

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Apical localization of Intercellular Adhesion Receptor (ICAM)-1 regulates the adhesion and guidance of leukocytes across polarized epithelial barriers. Here, we investigate the molecular mechanisms that determine ICAM-1 localization into apical membrane domains of polarized hepatic epithelial cells, and their effect on lymphocyte-hepatic epithelial cell interaction. We had previously shown that segregation of ICAM-1 into apical membrane domains, which form bile canaliculi and bile ducts in hepatic epithelial cells, requires basolateral-to-apical transcytosis. Searching for protein machinery potentially involved in ICAM-1 polarization we found that the SNARE-associated protein plasmolipin (PLLP) is expressed in the subapical compartment of hepatic epithelial cells in vitro and in vivo. BioID analysis of ICAM-1 revealed proximal interaction between this adhesion receptor and PLLP. ICAM-1 colocalized and interacted with PLLP during the transcytosis of the receptor. PLLP gene editing and silencing increased the basolateral localization and reduced the apical confinement of ICAM-1 without affecting apicobasal polarity of hepatic epithelial cells, indicating that ICAM-1 transcytosis is specifically impaired in the absence of PLLP. Importantly, PLLP depletion was sufficient to increase T-cell adhesion to hepatic epithelial cells. Such an increase depended on the epithelial cell polarity and ICAM-1 expression, showing that the epithelial transcytotic machinery regulates the adhesion of lymphocytes to polarized epithelial cells. Our findings strongly suggest that the polarized intracellular transport of adhesion receptors constitutes a new regulatory layer of the epithelial inflammatory response.

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Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge

Cited by 32 publications

References 42 publications

Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex

Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex

EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis

Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells

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