scholarly journals Cell behaviors regulated by guidance cues in collective migration of border cells

2011 ◽  
Vol 192 (3) ◽  
pp. 513-524 ◽  
Author(s):  
Minna Poukkula ◽  
Adam Cliffe ◽  
Rishita Changede ◽  
Pernille Rørth
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Cell Group ◽  
Border Cells ◽  
Collective Migration ◽  
Cell Behaviors ◽  
Guidance Cues ◽  
Guidance Receptors ◽  
Endothelial Growth Factor

Border cells perform a collective, invasive, and directed migration during Drosophila melanogaster oogenesis. Two receptor tyrosine kinases (RTKs), the platelet-derived growth factor/vascular endothelial growth factor–related receptor (PVR) and the epidermal growth factor receptor (EGFR), are important for reading guidance cues, but how these cues steer migration is not well understood. During collective migration, front, back, and side extensions dynamically project from individual cells within the group. We find that guidance input from both RTKs affects the presence and size of these extensions, primarily by favoring the persistence of front extensions. Guidance cues also control the productivity of extensions, specifically rendering back extensions nonproductive. Early and late phases of border cell migration differ in efficiency of forward cluster movement, although motility of individual cells appears constant. This is caused by differences in behavioral effects of the RTKs: PVR dominantly induces large persistent front extensions and efficient streamlined group movement, whereas EGFR does not. Thus, guidance receptors steer movement of this cell group by differentially affecting multiple migration-related features.

scholarly journals Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling

2020 ◽  
Vol 295 (29) ◽  
pp. 9917-9933 ◽  
Author(s):  
Michael D. Paul ◽  
Hana N. Grubb ◽  
Kalina Hristova
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Eph Receptor ◽  
Vital Cell ◽  
Cell Processes ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins that control vital cell processes such as cell growth, survival, and differentiation. There is a growing body of evidence that RTKs from different subfamilies can interact and that these diverse interactions can have important biological consequences. However, these heterointeractions are often ignored, and their strengths are unknown. In this work, we studied the heterointeractions of nine RTK pairs, epidermal growth factor receptor (EGFR)–EPH receptor A2 (EPHA2), EGFR–vascular endothelial growth factor receptor 2 (VEGFR2), EPHA2–VEGFR2, EPHA2–fibroblast growth factor receptor 1 (FGFR1), EPHA2–FGFR2, EPHA2–FGFR3, VEGFR2–FGFR1, VEGFR2–FGFR2, and VEGFR2–FGFR3, using a FRET-based method. Surprisingly, we found that RTK heterodimerization and homodimerization strengths can be similar, underscoring the significance of RTK heterointeractions in signaling. We discuss how these heterointeractions can contribute to the complexity of RTK signal transduction, and we highlight the utility of quantitative FRET for probing multiple interactions in the plasma membrane.

scholarly journals A novel localization based biosensor, SEDAR, visualizes spatio-temporal dynamics of activated Ras in endogenous Drosophila tissues

2018 ◽  
Author(s):  
Rishita Changede
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Real Time ◽  
Tyrosine Kinases ◽  
Temporal Dynamics ◽  
Three Dimensional ◽  
Growth Factor Receptor ◽  
Leading Edge ◽  
Border Cells ◽  
Spatio Temporal

AbstractChemokine signaling via growth factor receptor tyrosine kinases (RTKs) regulates development, differentiation, growth and disease implying that it is involved in a myriad of cellular processes. A single RTK, for example the Epidermal Growth Factor Receptor (EGFR), is used repeatedly for a multitude of developmental programs. Quantitative differences in magnitude and duration of RTK signaling can bring about different signaling outcomes. Understanding this complex RTK signals requires real time visualization of the signal. To visualize spatio-temporal signaling dynamics, a biosensor called SEnsitive Detection of Activated Ras (SEDAR) was developed. It is a localization-based sensor that binds to activated Ras directly downstream of the endogenous activated RTKs. This binding was reversible and SEDAR expression did not cause any detectable perturbation of the endogenous signal. Using SEDAR, endogenous guidance signaling was visualized during RTK mediated chemotaxis of border cells in Drosophila ovary. SEDAR localized to both the leading and rear end of the cluster but polarized at the leading edge of the cluster. Perturbation of RTKs that led to delays in forward migration of the cluster correlated with loss of SEDAR polarization in the cluster. Gliding or tumbling behavior of border cells was a directly related to the high or low magnitude of SEDAR polarization respectively, in the leading cell showing that signal polarization at the plasma membrane provided information for the migratory behavior. Further, SEDAR localization to the plasma membrane detected EGFR mediated signaling in five distinct developmental contexts. Hence SEDAR, a novel biosensor could be used as a valuable tool to study the dynamics of endogenous Ras activation in real time downstream of RTKs, in three-dimensional tissues, at an unprecedented spatial and temporal resolution.

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