scholarly journals Soluble αKlotho downregulates Orai1-mediated store-operated Ca2+ entry via PI3K-dependent signaling

2021 ◽  
Author(s):  
Ji-Hee Kim ◽  
Eun Young Park ◽  
Kyu-Hee Hwang ◽  
Kyu-Sang Park ◽  
Seong Jin Choi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Ion Homeostasis ◽  
Brefeldin A ◽  
Premature Aging ◽  
Tumor Cell Migration ◽  
Pi3k Inhibitors ◽  
Crac Channel ◽  
Vesicular Exocytosis ◽  
Phosphoinositide 3 Kinase

AbstractαKlotho is a type 1 transmembrane anti-aging protein. αKlotho-deficient mice have premature aging phenotypes and an imbalance of ion homeostasis including Ca2+ and phosphate. Soluble αKlotho is known to regulate multiple ion channels and growth factor-mediated phosphoinositide-3-kinase (PI3K) signaling. Store-operated Ca2+ entry (SOCE) mediated by pore-forming subunit Orai1 and ER Ca2+ sensor STIM1 is a ubiquitous Ca2+ influx mechanism and has been implicated in multiple diseases. However, it is currently unknown whether soluble αKlotho regulates Orai1-mediated SOCE via PI3K-dependent signaling. Among the Klotho family, αKlotho downregulates SOCE while βKlotho or γKlotho does not affect SOCE. Soluble αKlotho suppresses serum-stimulated SOCE and Ca2+ release-activated Ca2+ (CRAC) channel currents. Serum increases the cell-surface abundance of Orai1 via stimulating vesicular exocytosis of the channel. The serum-stimulated SOCE and cell-surface abundance of Orai1 are inhibited by the preincubation of αKlotho protein or PI3K inhibitors. Moreover, the inhibition of SOCE and cell-surface abundance of Orai1 by pretreatment of brefeldin A or tetanus toxin or PI3K inhibitors prevents further inhibition by αKlotho. Functionally, we further show that soluble αKlotho ameliorates serum-stimulated SOCE and cell migration in breast and lung cancer cells. These results demonstrate that soluble αKlotho downregulates SOCE by inhibiting PI3K-driven vesicular exocytosis of the Orai1 channel and contributes to the suppression of SOCE-mediated tumor cell migration.

Abstract 4410: Inhibition of cell surface polysialic acid biosynthesis modulates tumor cell migration.

2013 ◽  
Author(s):  
Bradley R. Springett ◽  
Yousef M.J. Al-Saraireh ◽  
Virginie Viprey ◽  
Mark Sutherland ◽  
Melanie Begouin ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Tumor Cell ◽  
Polysialic Acid ◽  
Acid Biosynthesis ◽  
Tumor Cell Migration

scholarly journals MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Marilyne Kpetemey ◽  
Subhamoy Dasgupta ◽  
Smrithi Rajendiran ◽  
Susobhan Das ◽  
Lee D. Gibbs ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Tumor Cell ◽  
Surface Expression ◽  
Annexin A2 ◽  
Cell Surface Expression ◽  
Tumor Cell Migration

scholarly journals Rab10-positive tubular structures represent a novel endocytic pathway that diverges from canonical macropinocytosis in RAW264 macrophages

2021 ◽  
Author(s):  
Katsuhisa Kawai ◽  
Arata Nishigaki ◽  
Seiji Moriya ◽  
Youhei Egami ◽  
Nobukazu Araki
Keyword(s):  
Cell Surface ◽  
Light Stimulus ◽  
Degradation Pathway ◽  
Endocytic Pathway ◽  
Tubular Structures ◽  
Myristate Acetate ◽  
Pi3k Inhibitors ◽  
Pi3k Activity ◽  
Golgi Region ◽  
Phosphoinositide 3 Kinase

AbstractUsing the optogenetic photo-manipulation of photoactivatable (PA)-Rac1, remarkable cell surface ruffling and the formation of a macropinocytic cup (premacropinosome) could be induced in the region of RAW264 macrophages irradiated with blue light due to the activation of PA-Rac1. However, the completion of macropinosome formation did not occur until Rac1 was deactivated by the removal of the light stimulus. Following PA-Rac1 deactivation, some premacropinosomes closed into intracellular macropinosomes, whereas many others transformed into long Rab10-positive tubules without forming typical macropinosomes. These Rab10-positive tubules moved centripetally towards the Golgi region along microtubules. Surprisingly, these Rab10-positive tubules did not contain any endosome/lysosome compartment markers, such as Rab5, Rab7, or LAMP1, suggesting that the Rab10-positive tubules were not part of the degradation pathway for lysosomes. These Rab10-positive tubules were distinct from recycling endosomal compartments, which are labeled with Rab4, Rab11, or SNX1. These findings suggested that these Rab10-positive tubules belonged to a novel, non-degradative, endocytic pathway. The formation of Rab10-positive tubules from premacropinosomes was also observed in control and phorbol myristate acetate (PMA)-stimulated macrophages, although their frequencies were low. Interestingly, the formation of Rab10-positive premacropinosomes and tubules was not inhibited by phosphoinositide 3-kinase (PI3K) inhibitors, while the classical macropinosome formation requires PI3K activity. Thus, this study provides evidence to support the existence of Rab10-positive tubules as a novel, non-degradative, endocytic pathway that diverges from canonical macropinocytosis.

scholarly journals CD44H regulates tumor cell migration on hyaluronate-coated substrate.

1992 ◽  
Vol 118 (4) ◽  
pp. 971-977 ◽  
Author(s):  
L Thomas ◽  
H R Byers ◽  
J Vink ◽  
I Stamenkovic
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Binding Capacity ◽  
Surface Glycoprotein ◽  
Cell Surface Receptor ◽  
Cell Surface Glycoprotein ◽  
Tumor Cell Migration ◽  
Coated Substrate ◽  
Direct Demonstration ◽  
Surface Receptor

CD44 is a broadly distributed cell surface glycoprotein expressed in different isoforms in various tissues and cell lines. One of two recently characterized human isoforms, CD44H, is a cell surface receptor for hyaluronate, suggesting a role in the regulation of cell-cell and cell-substrate interactions as well as of cell migration. While CD44H has been shown to mediate cell adhesion, direct demonstration that CD44H expression promotes cell motility has been lacking. In this work we show that a human melanoma cell line, stably transfected with CD44H, displays enhanced motility on hyaluronate-coated surfaces while transfectants expressing an isoform that does not bind hyaluronate, CD44E, fail to do so. Migration of CD44H-expressing transfectants is observed to be blocked by a soluble CD44-immunoglobulin fusion protein as well as by anti-CD44 antibody, and to depend on the presence of the cytoplasmic domain of CD44. However, cells expressing CD44H cytoplasmic deletion mutants retain significant binding capacity to hyaluronate-coated substrate. Taken together, our results provide direct evidence that CD44H plays a major role in regulating cell migration on hyaluronate-coated substrate.

scholarly journals Rab10-Positive Tubular Structures Represent a Novel Endocytic Pathway That Diverges From Canonical Macropinocytosis in RAW264 Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Katsuhisa Kawai ◽  
Arata Nishigaki ◽  
Seiji Moriya ◽  
Youhei Egami ◽  
Nobukazu Araki
Keyword(s):  
Cell Surface ◽  
Light Stimulus ◽  
Degradation Pathway ◽  
Endocytic Pathway ◽  
Tubular Structures ◽  
Myristate Acetate ◽  
Pi3k Inhibitors ◽  
Pi3k Activity ◽  
Golgi Region ◽  
Phosphoinositide 3 Kinase

Using the optogenetic photo-manipulation of photoactivatable (PA)-Rac1, remarkable cell surface ruffling and the formation of a macropinocytic cup (premacropinosome) could be induced in the region of RAW264 macrophages irradiated with blue light due to the activation of PA-Rac1. However, the completion of macropinosome formation did not occur until Rac1 was deactivated by the removal of the light stimulus. Following PA-Rac1 deactivation, some premacropinosomes closed into intracellular macropinosomes, whereas many others transformed into long Rab10-positive tubules without forming typical macropinosomes. These Rab10-positive tubules moved centripetally towards the perinuclear Golgi region along microtubules. Surprisingly, these Rab10-positive tubules did not contain any endosome/lysosome compartment markers, such as Rab5, Rab7, or LAMP1, suggesting that the Rab10-positive tubules were not part of the degradation pathway for lysosomes. These Rab10-positive tubules were distinct from recycling endosomal compartments, which are labeled with Rab4, Rab11, or SNX1. These findings suggested that these Rab10-positive tubules may be a part of non-degradative endocytic pathway that has never been known. The formation of Rab10-positive tubules from premacropinosomes was also observed in control and phorbol myristate acetate (PMA)-stimulated macrophages, although their frequencies were low. Interestingly, the formation of Rab10-positive premacropinosomes and tubules was not inhibited by phosphoinositide 3-kinase (PI3K) inhibitors, while the classical macropinosome formation requires PI3K activity. Thus, this study provides evidence to support the existence of Rab10-positive tubules as a novel endocytic pathway that diverges from canonical macropinocytosis.

scholarly journals Matrix metalloproteinase-2 activation modulates glioma cell migration

1997 ◽  
Vol 110 (19) ◽  
pp. 2473-2482
Author(s):  
E.I. Deryugina ◽  
M.A. Bourdon ◽  
G.X. Luo ◽  
R.A. Reisfeld ◽  
A. Strongin
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Surface Expression ◽  
Matrix Proteins ◽  
Matrix Metalloproteinase 2 ◽  
Cell Surface Expression ◽  
Blocking Antibody ◽  
Tumor Cell Migration ◽  
Adhesion Sites ◽  
Glioma Cell Migration

Stable transfection of U251.3 glioma cells with cDNA encoding MT-MMP-1 resulted in increased cell surface expression of MT-MMP-1 and TIMP-2, constitutive activation of MMP-2 proenzyme and increased collagen degradation. In tumor spheroid outgrowth assays, cell migration of MT-MMP-1 transfectants relative to control was enhanced on collagen and decreased on vitronectin and fibronectin. These effects were reversed by TIMP-2 and were not associated with any substantial changes in cell adhesion. Binding of U251.3 cells to the C-terminal domain of MMP-2 was specifically inhibited by anti-(alpha)vss3 integrin blocking antibody indicating that MMP-2 interacts with (alpha)vss3 through the enzyme's C-terminal portion at or near the integrin's matrix adhesion sites. We propose that these mechanisms could govern directed matrix degradation in the tumor cells' microenvironment by sequestration of active MMP-2 on the cell surface. Our data suggest that activation of MMP-2 and its proteolytic activity localized to the cell surface could differentially modulate tumor cell migration in response to particular matrix proteins by altering both composition of the extracellular matrix and expression of adhesion receptors on the cell surface.

A Possible Modulation Mechanism of Intramolecular and Intermolecular Interactions for NCAM Polysialylation and Cell Migration

2019 ◽  
Vol 19 (25) ◽  
pp. 2271-2282 ◽  
Author(s):  
Bo Lu ◽  
Xue-Hui Liu ◽  
Si-Ming Liao ◽  
Zhi-Long Lu ◽  
Dong Chen ◽  
...  
Keyword(s):  
Cell Migration ◽  
Intermolecular Interactions ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Intramolecular Interaction ◽  
Polysialic Acid ◽  
Tumor Cell Migration ◽  
Neural Cell Adhesion ◽  
Polybasic Domains ◽  
Novel Model

Polysialic acid (polySia) is a novel glycan that posttranslationally modifies neural cell adhesion molecules (NCAMs) in mammalian cells. Up-regulation of polySia-NCAM expression or NCAM polysialylation is associated with tumor cell migration and progression in many metastatic cancers and neurocognition. It has been known that two highly homologous mammalian polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST), can catalyze polysialylation of NCAM, and two polybasic domains, polybasic region (PBR) and polysialyltransferase domain (PSTD) in polySTs play key roles in affecting polyST activity or NCAM polysialylation. However, the molecular mechanisms of NCAM polysialylation and cell migration are still not entirely clear. In this minireview, the recent research results about the intermolecular interactions between the PBR and NCAM, the PSTD and cytidine monophosphate-sialic acid (CMP-Sia), the PSTD and polySia, and as well as the intramolecular interaction between the PBR and the PSTD within the polyST, are summarized. Based on these cooperative interactions, we have built a novel model of NCAM polysialylation and cell migration mechanisms, which may be helpful to design and develop new polysialyltransferase inhibitors.

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