scholarly journals Caenorhabditis elegans LET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells

PLoS Genetics ◽  
2021 ◽  
Vol 17 (10) ◽  
pp. e1009856
Author(s):  
Amalia Riga ◽  
Janine Cravo ◽  
Ruben Schmidt ◽  
Helena R. Pires ◽  
Victoria G. Castiglioni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Postembryonic Development ◽  
Epithelial Polarity ◽  
Adapter Protein ◽  
Cellular Processes ◽  
Directed Cell Migration ◽  
Seam Cell ◽  
Discs Large ◽  
Inducible Protein

The conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. In C. elegans, the Scrib ortholog LET-413 is essential for apical–basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is likely mediated largely by the junctional component DLG-1 discs large, which we demonstrate is also essential for directed outgrowth of the seam cells. Our data uncover multiple essential functions for LET-413 in larval development and show that the polarized outgrowth of the epithelial seam cells is controlled by LET-413 Scribble and DLG-1 Discs large.

scholarly journals Caenorhabditis elegansLET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells

2021 ◽  
Author(s):  
Amalia Riga ◽  
Janine Cravo ◽  
Ruben Schmidt ◽  
Helena R. Pires ◽  
Victoria G. Castiglioni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Postembryonic Development ◽  
Cell Outgrowth ◽  
C Elegans ◽  
Cellular Processes ◽  
Directed Cell Migration ◽  
Seam Cell ◽  
Discs Large ◽  
Rho Family Gtpases ◽  
Inducible Protein

AbstractThe conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. InC. elegans, the Scrib ortholog LET-413 is essential for apical–basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is mediated at least in part by the junctional component DLG-1 discs large, which appears to restrict protrusive activity to the apical domain. Finally, we demonstrate that the Rho-family GTPases CED-10 Rac and CDC-42 can regulate seam cell outgrowth and may also function downstream of LET-413. Our data uncover multiple essential functions for LET-413 in larval development and shed new light on the regulation of polarized outgrowth of the seam cells.

The regulation of cell migration by PTEN

2005 ◽  
Vol 33 (6) ◽  
pp. 1507-1508 ◽  
Author(s):  
N.R. Leslie ◽  
X. Yang ◽  
C.P. Downes ◽  
C.J. Weijer
Keyword(s):  
Cell Migration ◽  
Phosphatase Activity ◽  
Tumour Suppressor ◽  
Chromosome 10 ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Directed Cell Migration ◽  
Phosphoinositide 3 Kinase ◽  
Phosphatase And Tensin Homologue

In vertebrates, the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) regulates many cellular processes through its PtdIns(3,4,5)P3 lipid phosphatase activity, antagonizing PI3K (phosphoinositide 3-kinase) signalling. Given the important role of PI3Ks in the regulation of directed cell migration and the role of PTEN as an inhibitor of migration, it is somewhat surprising that data now indicate that PTEN is able to regulate cell migration independent of its lipid phosphatase activity. Here, we discuss the role of PTEN in the regulation of cell migration.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals Regulation of circular dorsal ruffles, macropinocytosis, and cell migration by RhoG and its exchange factor, Trio

2017 ◽  
Vol 28 (13) ◽  
pp. 1768-1781 ◽  
Author(s):  
Alejandra Valdivia ◽  
Silvia M. Goicoechea ◽  
Sahezeel Awadia ◽  
Ashtyn Zinn ◽  
Rafael Garcia-Mata
Keyword(s):  
Cell Migration ◽  
Mammalian Cells ◽  
Dorsal Surface ◽  
Receptor Internalization ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Unique Type ◽  
Exchange Factor ◽  
Cellular Processes

Circular dorsal ruffles (CDRs) are actin-rich structures that form on the dorsal surface of many mammalian cells in response to growth factor stimulation. CDRs represent a unique type of structure that forms transiently and only once upon stimulation. The formation of CDRs involves a drastic rearrangement of the cytoskeleton, which is regulated by the Rho family of GTPases. So far, only Rac1 has been consistently associated with CDR formation, whereas the role of other GTPases in this process is either lacking or inconclusive. Here we show that RhoG and its exchange factor, Trio, play a role in the regulation of CDR dynamics, particularly by modulating their size. RhoG is activated by Trio downstream of PDGF in a PI3K- and Src-dependent manner. Silencing RhoG expression decreases the number of cells that form CDRs, as well as the area of the CDRs. The regulation of CDR area by RhoG is independent of Rac1 function. In addition, our results show the RhoG plays a role in the cellular functions associated with CDR formation, including macropinocytosis, receptor internalization, and cell migration. Taken together, our results reveal a novel role for RhoG in the regulation of CDRs and the cellular processes associated with their formation.

scholarly journals Actin-dependent Lamellipodia Formation and Microtubule-dependent Tail Retraction Control-directed Cell Migration

2000 ◽  
Vol 11 (9) ◽  
pp. 2999-3012 ◽  
Author(s):  
Christoph Ballestrem ◽  
Bernhard Wehrle-Haller ◽  
Boris Hinz ◽  
Beat A. Imhof
Keyword(s):  
Cell Migration ◽  
Cell Body ◽  
Actin Polymerization ◽  
Green Fluorescence Protein ◽  
Time Lapse ◽  
Dependent Manner ◽  
Directed Cell Migration ◽  
Cell Front ◽  
Fluorescence Protein

Migrating cells are polarized with a protrusive lamella at the cell front followed by the main cell body and a retractable tail at the rear of the cell. The lamella terminates in ruffling lamellipodia that face the direction of migration. Although the role of actin in the formation of lamellipodia is well established, it remains unclear to what degree microtubules contribute to this process. Herein, we have studied the contribution of microtubules to cell motility by time-lapse video microscopy on green flourescence protein-actin- and tubulin-green fluorescence protein–transfected melanoma cells. Treatment of cells with either the microtubule-disrupting agent nocodazole or with the stabilizing agent taxol showed decreased ruffling and lamellipodium formation. However, this was not due to an intrinsic inability to form ruffles and lamellipodia because both were restored by stimulation of cells with phorbol 12-myristate 13-acetate in a Rac-dependent manner, and by stem cell factor in melanoblasts expressing the receptor tyrosine kinase c-kit. Although ruffling and lamellipodia were formed without microtubules, the microtubular network was needed for advancement of the cell body and the subsequent retraction of the tail. In conclusion, we demonstrate that the formation of lamellipodia can occur via actin polymerization independently of microtubules, but that microtubules are required for cell migration, tail retraction, and modulation of cell adhesion.

scholarly journals Optogenetic toolkit reveals the role of Ca2+sparklets in coordinated cell migration

2016 ◽  
Vol 113 (21) ◽  
pp. 5952-5957 ◽  
Author(s):  
Jin Man Kim ◽  
Minji Lee ◽  
Nury Kim ◽  
Won Do Heo
Keyword(s):  
Cell Migration ◽  
Directed Cell Migration ◽  
Clear Link ◽  
Rear Part ◽  
Voltage Dependent ◽  
Morphological Polarity ◽  
Lamellipodia Formation ◽  
Migrating Cells

Cell migration is controlled by various Ca2+signals. Local Ca2+signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. However, little is known about how local Ca2+signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca2+signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca2+sparklets mediated by L-type voltage-dependent Ca2+channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca2+influx acts as an essential transducer in establishing a global front-to-rear increasing Ca2+gradient. This asymmetrical Ca2+gradient is crucial for maintaining front–rear morphological polarity by restricting spontaneous lamellipodia formation in the rear part of migrating cells. Collectively, our findings demonstrate a clear link between local Ca2+sparklets and front–rear coordination during directed cell migration.

Drink or drive: competition between macropinocytosis and cell migration

2015 ◽  
Vol 43 (1) ◽  
pp. 129-132 ◽  
Author(s):  
Douwe M. Veltman
Keyword(s):  
Cell Migration ◽  
High Resolution ◽  
Cell Motility ◽  
Actin Filaments ◽  
Cellular Processes ◽  
Heavy Drinkers ◽  
Molecular Components ◽  
High Resolution Microscopy ◽  
Wave Complex

The cytoskeleton is utilized for a variety of cellular processes, including migration, endocytosis and adhesion. The required molecular components are often shared between different processes, but it is not well understood how the cells balance their use. We find that macropinocytosis and cell migration are negatively correlated. Heavy drinkers move only slowly and vice versa, fast cells do not take big gulps. Both processes are balanced by the lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3). Elevated PIP3 signalling causes a shift towards macropinocytosis and inhibits motility by redirecting the SCAR/WAVE complex, a major nucleator of actin filaments. High resolution microscopy shows that patches with high levels of PIP3 recruit SCAR/WAVE on their periphery, resulting in circular ruffle formation and engulfment. Results shed new light on the role of PIP3, which is commonly thought to promote cell motility.

scholarly journals Connexin43 controls N-cadherin transcription during collective cell migration

2017 ◽  
Author(s):  
Maria Kotini ◽  
Elias H. Barriga ◽  
Jonathan Leslie ◽  
Marc Gentzel ◽  
Alexandra Schambony ◽  
...  
Keyword(s):  
Cell Migration ◽  
Gap Junctions ◽  
Neural Crest ◽  
Cancer Metastasis ◽  
Embryonic Cell ◽  
Collective Cell Migration ◽  
List Type ◽  
Cellular Processes ◽  
Physiological Processes

AbstractConnexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a mystery. To shed light on this, we investigated the role of Connexin43 in collective cell migration during embryo development using the neural crest, an embryonic cell population whose migratory behavior has been likened to cancer invasion. We discovered that Connexin43 is required for contact inhibition of locomotion by directly regulating the transcription of N-cadherin. For this function, the Connexin43 carboxy tail interacts with Basic Transcription Factor 3, which mediates its translocation to the nucleus. Together, they bind to the n-cad promotor regulating n-cad transcription. Thus, we uncover an unexpected, gap junction-independent role for Connexin43 in collective migration that illustrates the possibility that connexins, in general, may be important for a wide variety of cellular processes that we are only beginning to understand.HighlightsCx43 regulates collective directional migration of neural crest cellsCx43 carboxy tail controls cell polarity via n-cad regulationCx43 carboxy tail localises at the nucleus and that depends on BTF3BTF3 and Cx43 carboxy tail directly interact to bind and regulate n-cad promoter activity

scholarly journals Epidermal PAR-6 and PKC-3 are essential for postembryonic development of Caenorhabditis elegans and control non-centrosomal microtubule organization

2020 ◽  
Author(s):  
Victoria G. Castiglioni ◽  
Helena R. Pires ◽  
Rodrigo Rosas Bertolini ◽  
Amalia Riga ◽  
Jana Kerver ◽  
...  
Keyword(s):  
Cell Types ◽  
Postembryonic Development ◽  
Microtubule Organization ◽  
Par Proteins ◽  
C Elegans ◽  
Seam Cell ◽  
Broad Variety ◽  
Animal Growth ◽  
Inducible Protein ◽  
And Control

AbstractThe cortical polarity regulators PAR-6, PKC-3 and PAR-3 are essential for the polarization of a broad variety of cell types in multicellular animals, from the first asymmetric division of the C. elegans zygote to apical–basal polarization of epithelial cells. In C. elegans, the roles of the PAR proteins in embryonic development have been extensively studied, yet little is known about their functions during larval development. Using auxin-inducible protein depletion, we here show that PAR-6 and PKC-3, but not PAR-3, are essential for postembryonic development. We also demonstrate that PAR-6 and PKC-3 are required in the epidermal epithelium to support animal growth and molting, and the proper timing and pattern of seam cell divisions. Finally, we uncovered a novel role for PAR-6 in controlling the organization of non-centrosomal microtubule arrays in the epidermis. PAR-6 was required for the localization of the microtubule organizer NOCA-1/Ninein, and microtubule defects in a noca-1 mutant are highly similar to those caused by epidermal PAR-6 depletion. As NOCA-1 physically interacts with PAR-6, we propose that PAR-6 promotes non-centrosomal microtubule organization through localization of NOCA-1/Ninein.SummaryUsing inducible protein degradation, we show that PAR-6 and PKC-3/aPKC are essential for postembryonic development of C. elegans and control the organization of non-centrosomal microtubule bundles in the epidermis, likely through recruitment of NOCA-1/Ninein.

scholarly journals Epidermal PAR-6 and PKC-3 are essential for larval development of C. elegans and organize non-centrosomal microtubules

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Victoria G Castiglioni ◽  
Helena R Pires ◽  
Rodrigo Rosas Bertolini ◽  
Amalia Riga ◽  
Jana Kerver ◽  
...  
Keyword(s):  
Larval Development ◽  
Cell Types ◽  
Postembryonic Development ◽  
Microtubule Organization ◽  
Par Proteins ◽  
C Elegans ◽  
Seam Cell ◽  
Broad Variety ◽  
Animal Growth ◽  
Inducible Protein

The cortical polarity regulators PAR-6, PKC-3, and PAR-3 are essential for the polarization of a broad variety of cell types in multicellular animals. In C. elegans, the roles of the PAR proteins in embryonic development have been extensively studied, yet little is known about their functions during larval development. Using inducible protein degradation, we show that PAR-6 and PKC-3, but not PAR-3, are essential for postembryonic development. PAR-6 and PKC-3 are required in the epidermal epithelium for animal growth, molting, and the proper pattern of seam-cell divisions. Finally, we uncovered a novel role for PAR-6 in organizing non-centrosomal microtubule arrays in the epidermis. PAR-6 was required for the localization of the microtubule organizer NOCA-1/Ninein, and defects in a noca-1 mutant are highly similar to those caused by epidermal PAR-6 depletion. As NOCA-1 physically interacts with PAR-6, we propose that PAR-6 promotes non-centrosomal microtubule organization through localization of NOCA-1/Ninein.

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