scholarly journals Intracellular pH gradients in migrating cells

2011 ◽  
Vol 300 (3) ◽  
pp. C490-C495 ◽  
Author(s):  
Christine Martin ◽  
Stine F. Pedersen ◽  
Albrecht Schwab ◽  
Christian Stock

Cell polarization along the axis of movement is required for migration. The localization of proteins and regulators of the migratory machinery to either the cell front or its rear results in a spatial asymmetry enabling cells to simultaneously coordinate cell protrusion and retraction. Protons might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pHi) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of pHi, the Na+/H+exchanger NHE1, is essential for cell migration and accumulates at the cell front. Here, we test the hypothesis that the uneven distribution of NHE1 activity creates a pHigradient in migrating cells. Using the pH-sensitive fluorescent dye BCECF, pHiwas measured in five cell lines (MV3, B16V, NIH3T3, MDCK-F1, EA.hy926) along the axis of movement. Differences in pHibetween the front and the rear end (ΔpHifront-rear) were present in all cell lines, and inhibition of NHE1 either with HOE642 or by absence of extracellular Na+caused the pHigradient to flatten or disappear. In conclusion, pHigradients established by NHE1 activity exist along the axis of movement.

2019 ◽  
Author(s):  
Adan Olguin-Olguin ◽  
Anne Aalto ◽  
Benoît Maugis ◽  
Michal Reichman-Fried ◽  
Erez Raz

The mechanisms facilitating the establishment of front-rear polarity in migrating cells are not fully understood, in particular in the context of bleb-driven directional migration. To gain further insight into this issue we utilized the migration of zebrafish primordial germ cells (PGCs) as an in vivo model. We followed the molecular and morphological cascade that converts apolar cells into polarized bleb-forming motile cells and analyzed the cross dependency among the different cellular functions we identified. Our results underline the critical role of antagonistic interactions between the front and the rear, in particular the role of biophysical processes including formation of barriers and transport of specific proteins to the back of the cell. These interactions direct the formation of blebs to a specific part of the cell that is specified as the cell front. In this way, spontaneous cell polarization facilitates non-directional cell motility and when biased by chemokine signals leads to migration towards specific locations.


1992 ◽  
Vol 116 (5) ◽  
pp. 1157-1166 ◽  
Author(s):  
U Euteneuer ◽  
M Schliwa

Locomoting cells are characterized by a pronounced external and internal anterior-posterior polarity. One of the events associated with cell polarization at the onset of locomotion is a shift of the centrosome, or MTOC, ahead of the nucleus. This position is believed to be of strategic importance for directional cell movement and cell polarity. We have used BSC-1 cells at the edge of an in vitro wound to clarify the causal relationship between MTOC position and the initiation of cell polarization. We find that pronounced cell polarization (the extension of a lamellipod) can take place in the absence of MTOC repositioning or microtubules. Conversely, MTOCs will reposition even after lamellar extension and cell polarization have occurred. Repositioning requires microtubules that extend to the cell periphery and is independent of selective detyrosination of microtubules extending towards the cell front. Significantly, MTOCs maintain, or at least attempt to maintain, a position at the cell's centroid. This is most clearly demonstrated in wounded monolayers of enucleated cells where the MTOC closely follows the centroid position. We suggest that the primary response to the would is the biased extension of a lamellipod, which can occur in the absence of microtubules and MTOC repositioning. Lamellipod extension leads to a shift of the cell's centroid towards the wound. The MTOC, in an attempt to maintain a position near the cell center, will follow. This will automatically put the MTOC ahead of the nucleus in the vast majority of cells. The nucleus as a reference for MTOC position may not be as meaningful as previously thought.


2021 ◽  
Vol 118 (7) ◽  
pp. e2018480118
Author(s):  
Adan Olguin-Olguin ◽  
Anne Aalto ◽  
Benoît Maugis ◽  
Aleix Boquet-Pujadas ◽  
Dennis Hoffmann ◽  
...  

To study the mechanisms controlling front-rear polarity in migrating cells, we used zebrafish primordial germ cells (PGCs) as an in vivo model. We find that polarity of bleb-driven migrating cells can be initiated at the cell front, as manifested by actin accumulation at the future leading edge and myosin-dependent retrograde actin flow toward the other side of the cell. In such cases, the definition of the cell front, from which bleb-inhibiting proteins such as Ezrin are depleted, precedes the establishment of the cell rear, where those proteins accumulate. Conversely, following cell division, the accumulation of Ezrin at the cleavage plane is the first sign for cell polarity and this aspect of the cell becomes the cell back. Together, the antagonistic interactions between the cell front and back lead to a robust polarization of the cell. Furthermore, we show that chemokine signaling can bias the establishment of the front-rear axis of the cell, thereby guiding the migrating cells toward sites of higher levels of the attractant. We compare these results to a theoretical model according to which a critical value of actin treadmilling flow can initiate a positive feedback loop that leads to the generation of the front-rear axis and to stable cell polarization. Together, our in vivo findings and the mathematical model, provide an explanation for the observed nonoriented migration of primordial germ cells in the absence of the guidance cue, as well as for the directed migration toward the region where the gonad develops.


2020 ◽  
Author(s):  
Satsuki Murakami ◽  
Susumu Suzuki ◽  
Ichiro Hanamura ◽  
Kazuhiro Yoshikawa ◽  
Ryuzo Ueda ◽  
...  

2010 ◽  
Vol 49 (S 01) ◽  
pp. S64-S68
Author(s):  
E. Dikomey

SummaryIonising irradiation acts primarily via induction of DNA damage, among which doublestrand breaks are the most important lesions. These lesions may lead to lethal chromosome aberrations, which are the main reason for cell inactivation. Double-strand breaks can be repaired by several different mechanisms. The regulation of these mechanisms appears be fairly different for normal and tumour cells. Among different cell lines capacity of doublestrand break repair varies by only few percents and is known to be determined mostly by genetic factors. Knowledge about doublestrand break repair mechanisms and their regulation is important for the optimal application of ionising irradiation in medicine.


2019 ◽  
Vol 7 (4) ◽  
pp. 91-96
Author(s):  
Isra'a Al-sobhi ◽  
◽  
Rawan Al-Ghabban ◽  
Soad Shaker Ali ◽  
Jehan Al-Amri ◽  
...  

Author(s):  
Joshi Vedamurthy ◽  
Shivakumar Inamdar ◽  
Ankit Acharya ◽  
Rajesh Kowti

In this project, in vitro absorption enhancement activity of P-gp substrates Fexofenadine (Fx) and Ciprofloxacin (Cp) were evaluated in everted rat gut sac model and Caco-2 cell lines. Verapamil was used as P-gp inhibitor. Piper betel, Trachyspermum ammi, Plumbago zeylanica, Trikatu, Moringaoleifera, Murraya koenigii,  Ferulafoitida  Zingiber officinale, Cheilocostus speciosus, Capsicum frutescens Operculina turpethum Holarrhena antidysenterica Mesuaferrea, Tinospora cordifolia,  and Picrorhiza kurroa, were selected and extracted with 99% alcohol and fresh juices of Citrus limon, Punica granatum seeds were also studied. In-vitro studies depicted that Fexofenadine and Ciprofloxacin absorption was increased greater than 20% in the presence of Operculinaturpethum, Capsicum frutescens, Holarrhena Antidysenterica, Tinospora cordifolia, Trikatu, Trachyspermum ammi, Plumbago zeylanica. The flux of the ciprofloxacin transport was in the range of 9-23 mcg/min and Papp         2.6 × 10-5 cm/sec to 4.1 × 10-5  cm/sec whereas Fexofenadine flux was in the range of 2-7.7 mcg/min and Papp 4.16 × 10–6 cm/sec to 1.62 ×       10-5 cm/sec.  In vitro antimicrobial activity of ciprofloxacin on selected microbes in presence of extracts also depicted synergistic activity. Histological studies revealed that there is no significant variation observed in the isolated sac in presence of the extracts. CaCo2 cell lines studies showed that, formulation enhanced the absorption of fexofenadine greater than 50%. Tablets were prepared and evaluated using the plant extracts which yielded >20% absorption enhancement of the substrates. In conclusion, tablet formulation containing the alcoholic extracts of Trachyspermum ammi, Plumbago zylanicum, Capsicum frutescens, Operculina turpethum, Holarrhena Antidysenterica, Tinospora cordifolia and Trikatu can act as an absorption enhancer for fexofenadine and ciprofloxacin. The mechanism of action of these herbs could be due to    P-gp inhibition. Further clinical studies are needed to prove its efficacy in humans.     


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