Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells

Jeon, Taeck J.; Lee, Dai-Jen; Lee, Susan; Weeks, Gerald; Firtel, Richard A.

doi:10.1083/jcb.200705068

Cited by 61 publications

(90 citation statements)

References 42 publications

(71 reference statements)

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“…1A; whose activity is crucial for cytokinesis in Dictyostelium (Faix et al, 1996;Weber et al, 1999). Recent studies have shown that cortexillins are involved in directional cell migration by interacting with Rac and Rap1 signaling pathways (Jeon et al, 2007a;. In this study, we examined the morphology and ability of mutant strains lacking cortexillins to polarize and chemotax up a chemoattractant gradient.…”

Section: Resultsmentioning

confidence: 99%

“…The chemotaxis towards cAMP and changes in the subcellular localization of proteins in response to chemoattractant stimulation were examined as described previously (Jeon et al, 2007a;Sasaki et al, 2004). The aggregation competent cells were plated on glass-bottomed microwell plates, and then a micropipette filled with 150 µM cMP was positioned near the cells to stimulate them.…”

Section: Development and Chemotaxis Analysismentioning

confidence: 99%

“…The quantitation of membrane or cortical localization of GFP fusion proteins was performed as described previously (Cha et al, 2010;Jeon et al, 2007a;Sasaki et al, 2004). The aggregation competent cells were allowed to adhere to the plate for 10 min.…”

Section: Quantitation Analysis Of Gfp Fusion Proteinsmentioning

confidence: 99%

“…Recent reports have demonstrated that cortexillin I is involved in cell migration by negatively regulating cortical localization of RapGAP1 in Dictyostelium. Cells lacking both cortexillins exhibit constitutive and uniform RapGAP1 cortical localization during chemotaxis, leading to a reduced chemoattractantmediated Rap1 activation level (Jeon et al, 2007a;. Cortexillin I is an F-actin bundling protein containing three domains (Faix, 2002;Faix et al, 1996;Weber et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…For expression of GFP-cortexillin I, the full coding sequence of the cortexillin I cDNA was generated by RT-PCR and cloned into the BglIIXhoI site of expression vector EXP-4(+) containing a GFP fragment. The expression plasmids for GFP-ArpD, GFP-coronin, and GFP-PhdA were described previously (Jeon et al, 2007a). The plasmids were transformed into KAx-3 or ctxA -/Bcells and the transformants were maintained in 20 µg/ml G418.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Localization of the Actin-Bundling Protein Cortexillin I during Cell Migration

Cha

Jeon

2011

Molecules and Cells

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Cortexillins are actin-bundling proteins that play a critical role in regulating cell morphology and actin cytoskeleton reorganization in Dictyostelium. Here, we investigated dynamic subcellular localization of cortexillin I in chemotaxing Dictyostelium cells. Most of the cortexillin I was enriched on the lateral sides of moving cells. Upon chemoattractant stimulation, cortexillin I was rapidly released from the cortex followed by a transient translocation to the cell cortex with a peak at ~5 s and a subsequent decrease to basal levels, indicating that localization of cor-texillin I at the cortex in chemotaxing cells is controlled by two more signaling components, one for the initial delocalization from the cortex and another for the translocation to the cortex ~5 s after chemoattractant stimulation. Loss of cortexillins leads to reduced cell polarity and an in-creased number of lateral pseudopodia during chemotaxis, suggesting that cortexillins play an inhibitory role in producing pseudopodia along the lateral sides of the cell. Cells lacking cortexillins displayed extended chemoattrac-tantmediated Arp2/3 complex translocation kinetics to the cortex. Our present study provides a new insight into the function of cortexillins during reorganization of the actin cytoskeleton and cell migration.

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Section: Resultsmentioning

confidence: 99%

Section: Development and Chemotaxis Analysismentioning

confidence: 99%

Section: Quantitation Analysis Of Gfp Fusion Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamic Localization of the Actin-Bundling Protein Cortexillin I during Cell Migration

Cha

Jeon

2011

Molecules and Cells

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Progression of mouse skin carcinogenesis is associated with the orchestrated deregulation of mir‐200 family members, mir‐205 and their common targets

Skourti

Logotheti

Kontos

et al. 2015

Molecular Carcinogenesis

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MicroRNAs are small, non-coding RNAs which regulate post-transcriptionally hundreds of target mRNAs. Given that their expression is deregulated in several cancer types, they represent potential diagnostic, prognostic, and predictive biomarkers, as well as next-generation therapeutic targets. Nevertheless, the involvement of miRNAs in non-melanoma skin cancer, a cancer type with increasing prevalence, is not extensively studied, and their comprehensive characterization as regard to the initiation, promotion, and progression stages is missing. To this end, we exploited a well-established multistage mouse skin carcinogenesis model in order to identify miRNAs consistently implicated in different stages of skin carcinogenesis. The cell lines comprising this model were subjected to miRNA expression profiling using microarrays, followed by bioinformatics analysis and validation with Q-PCR, as well as treatment with miRNA modulators. We showed that among all deregulated miRNAs in our system, only a functionally coherent group consisting of the miR-200 family members and miR-205-5p displays a pattern of progressive co-downregulation from the early toward the most aggressive stages of carcinogenesis. Their overlapping, co-regulated putative targets are potentially inter-associated and, of these, the EMT-related Rap1a is overexpressed toward aggressive stages. Ectopic expression of miR-205-5p in spindle cancer cells reduces Rap1a, mitigates cell invasiveness, decreases proliferation, and delays tumor onset. We conclude that deregulation of this miRNA group is primarily associated with aggressive phenotypes of skin cancer cells. Restoration of the miR-205-5p member of this group in spindle cells reduces the expression of critical, co-regulated targets that favor cancer progression, thus reversing the EMT characteristics. © 2015 Wiley Periodicals, Inc.

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Spatiotemporal Regulation of Ras-GTPases During Chemotaxis

Sasaki

Firtel

2009

Methods in Molecular Biology

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Many eukaryotic cells can elicit intracellular signaling relays to produce pseudopodia and move up to the chemoattractant gradient (chemotaxis) or move randomly in the absence of extracellular stimuli and nutrients (random movement). A precise spatiotemporal regulation of Ras-GTPases, such as Ras and Rap, is crucial to induce pseudopodia formation and cellular adhesion during the chemotaxis and random movement. Here, we describe biochemical and real-time imaging methods for using Dictyostelium to understand the signaling events important for chemotaxis and random cell movement. The chapter includes (1) a biochemical method to assess Ras and Rap1 activation in response to chemoattractant, (2) an imaging method to detect endogenous Ras and Rap1 activation in moving cells, and (3) a simultaneous imaging method to decipher the precise order and localization of these signaling events. With a combination of powerful Dictyostelium genetics, these methods will facilitate to elucidate a dynamic activation of Ras proteins and their inter relay with other signaling molecules during chemotaxis and random movement.

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Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells

Cited by 61 publications

References 42 publications

Dynamic Localization of the Actin-Bundling Protein Cortexillin I during Cell Migration

Dynamic Localization of the Actin-Bundling Protein Cortexillin I during Cell Migration

Progression of mouse skin carcinogenesis is associated with the orchestrated deregulation of mir‐200 family members, mir‐205 and their common targets

Spatiotemporal Regulation of Ras-GTPases During Chemotaxis

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