cellular protrusion
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2021 ◽  
Vol 118 (18) ◽  
pp. e2023829118
Author(s):  
Ana Martins Figueiredo ◽  
Pedro Barbacena ◽  
Ana Russo ◽  
Silvia Vaccaro ◽  
Daniela Ramalho ◽  
...  

Sprouting angiogenesis is fundamental for development and contributes to cancer, diabetic retinopathy, and cardiovascular diseases. Sprouting angiogenesis depends on the invasive properties of endothelial tip cells. However, there is very limited knowledge on how tip cells invade into tissues. Here, we show that endothelial tip cells use dactylopodia as the main cellular protrusion for invasion into nonvascular extracellular matrix. We show that dactylopodia and filopodia protrusions are balanced by myosin IIA (NMIIA) and actin-related protein 2/3 (Arp2/3) activity. Endothelial cell-autonomous ablation of NMIIA promotes excessive dactylopodia formation in detriment of filopodia. Conversely, endothelial cell-autonomous ablation of Arp2/3 prevents dactylopodia development and leads to excessive filopodia formation. We further show that NMIIA inhibits Rac1-dependent activation of Arp2/3 by regulating the maturation state of focal adhesions. Our discoveries establish a comprehensive model of how endothelial tip cells regulate its protrusive activity and will pave the way toward strategies to block invasive tip cells during sprouting angiogenesis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mauricio Garrido ◽  
Diego Morales ◽  
María Paz Saldías ◽  
Christian Fernández ◽  
Veronica Villalobos ◽  
...  

Abstract Background This study aimed to evaluate the biological response of human apical papilla cells to different calcium hydroxide formulations and three tricalcium silicate-based materials. Methods Primary cells were obtained from explants of young immature premolars. 20,000 cells adhered for 24 h over discs of Biodentine™, ProRoot®MTA, BioRoot®RCS and calcium hydroxide mixed either with sodium chloride 0.9%w/v or polyethylene glycol and UltraCal® were used to evaluate cell adhesion by scanning electron microscopy and cell viability by MTT assay. Results Cells adhered to ProRoot®MTA showed an increase of F-actin like protrusions, suggesting bioactivity. Cells adhered to UltraCal® show protrusion such as filopodia. On the contrary, cells adhered to BioRoot®RCS showed no signs of any cellular protrusion. Regarding viability between the materials, we found a higher percentage of viability in cells cultured over discs of Biodentine™ and ProRoot®MTA. Conclusion ProRoot®MTA and Biodentine™ exhibit a better cellular response of human apical papilla cells in vitro conditions compared to BioRoot® and calcium hydroxide diluted in sodium chloride.


2020 ◽  
Author(s):  
Ana M. Figueiredo ◽  
Pedro Barbacena ◽  
Ana Russo ◽  
Silvia Vaccaro ◽  
Daniela Ramalho ◽  
...  

AbstractSprouting angiogenesis is fundamental for development and contributes to multiple diseases, including cancer, diabetic retinopathy and cardiovascular diseases. Sprouting angiogenesis depends on the invasive properties of endothelial tip cells. However, there is very limited knowledge on the mechanisms that endothelial tip cells use to invade into tissues. Here, we prove that endothelial tip cells use long lamellipodia projections (LLPs) as the main cellular protrusion for invasion into non-vascular extracellular matrix. We show that LLPs and filopodia protrusions are balanced by myosin-IIA (MIIA) and actin-related protein 2/3 (Arp2/3) activity. Endothelial cell-autonomous ablation of MIIA promotes excessive LLPs formation in detriment of filopodia. Conversely, endothelial cell-autonomous ablation of Arp2/3 prevents LLPs development and leads to excessive filopodia formation. We further show that MIIA inhibits Rac1-dependent activation of Arp2/3, by regulating the maturation state of focal adhesions. Our discoveries establish the first comprehensive model of how endothelial tip cells regulate its protrusive activity and will pave the way towards new strategies to block invasive tip cells during sprouting angiogenesis.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Aaron M. Muscarella ◽  
Wei Dai ◽  
Patrick G. Mitchell ◽  
Weijie Zhang ◽  
Hai Wang ◽  
...  

Abstract Migration and invasion are key properties of metastatic cancer cells. These properties can be acquired through intrinsic reprogramming processes such as epithelial-mesenchymal transition. In this study, we discovered an alternative “migration-by-tethering” mechanism through which cancer cells gain the momentum to migrate by adhering to mesenchymal stem cells or osteoblasts. This tethering is mediated by both heterotypic adherens junctions and gap junctions, and leads to a unique cellular protrusion supported by cofilin-coated actin filaments. Inhibition of gap junctions or depletion of cofilin reduces migration-by-tethering. We observed evidence of these protrusions in bone segments harboring experimental and spontaneous bone metastasis in animal models. These data exemplify how cancer cells may acquire migratory ability without intrinsic reprogramming. Furthermore, given the important roles of osteogenic cells in early-stage bone colonization, our observations raise the possibility that migration-by-tethering may drive the relocation of disseminated tumor cells between different niches in the bone microenvironment.


Open Biology ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 200039
Author(s):  
Dae Seok Eom

Understanding the mechanisms of cell-to-cell communication is one of the fundamental questions in biology and medicine. In particular, long-range signalling where cells communicate over several cell diameters is vital during development and homeostasis. The major morphogens, their receptors and intracellular signalling cascades have largely been identified; however, there is a gap in our knowledge of how such signalling factors are propagated over a long distance. In addition to the diffusion-based propagation model, new modalities of disseminating signalling molecules have been identified. It has been shown that cells can communicate with direct contact through long, thin cellular protrusions between signal sending and receiving cells at a distance. Recent studies have revealed a type of cellular protrusion termed ‘airinemes’ in zebrafish pigment cell types. They share similarities with previously reported cellular protrusions; however, they also exhibit distinct morphology and features. Airinemes are indispensable for pigment pattern development by mediating long-distance Delta-Notch signalling between different pigment cell types. Notably, airineme-mediated signalling is dependent on skin-resident macrophages. Key findings of airineme-mediated intercellular signalling in pattern development, their interplay with macrophages and their implications for the understanding of cellular protrusion-mediated intercellular communication will be discussed.


2020 ◽  
Author(s):  
Qiannan Deng ◽  
Ye Sing Tan ◽  
Liang Yuh Chew ◽  
Hongyan Wang

SUMMARYThe ability of stem cells to switch between quiescence and proliferation is crucial for tissue homeostasis and regeneration. Drosophila quiescent neural stem cells (NSCs) extend a primary cellular protrusion from the cell body prior to their reactivation. However, the structure and function of this protrusion are not well established. In this study, we show that in the primary protrusion of quiescent NSCs microtubules are predominantly acentrosomal and oriented plus-end-out, distal to the cell body. We have identified Mini Spindles (Msps)/XMAP215 as a key regulator of NSC reactivation and acentrosomal microtubule assembly in quiescent NSCs. We show that E-cadherin, a cell adhesion molecule, is localized to NSC-neuropil contact points, in a Msps-dependent manner, and is intrinsically required for NSC reactivation. Our study demonstrates a novel mechanism by which Msps-dependent microtubule assembly in the primary protrusion of quiescent NSCs targets E-cadherin to NSC-neuropil contact sites to promote NSC reactivation. We propose that the neuropil functions as a new niche for promoting NSC reactivation, which may be a general paradigm in mammalian systems.


2019 ◽  
Vol 36 (5) ◽  
pp. 421-431
Author(s):  
Mitchell A. Johnson ◽  
Rachelle Kleinberger ◽  
Ali Abu Helal ◽  
Nicole Latchminarine ◽  
Ahmed Ayyash ◽  
...  

2019 ◽  
Vol 116 (3) ◽  
pp. 121a ◽  
Author(s):  
Sayak Bhattacharya ◽  
Yuchuan Miao ◽  
Peter N. Devreotes ◽  
Pablo A. Iglesias

2018 ◽  
Vol 217 (6) ◽  
pp. 2205-2221 ◽  
Author(s):  
Markus Brown ◽  
Louise A. Johnson ◽  
Dario A. Leone ◽  
Peter Majek ◽  
Kari Vaahtomeri ◽  
...  

Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.


2017 ◽  
Author(s):  
Vanja Dakic ◽  
Juliana Minardi Nascimento ◽  
Rafaela Costa Sartore ◽  
Renata de Moraes Maciel ◽  
Draulio B. de Araujo ◽  
...  

AbstractDimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention. Historical and technical restrictions impaired understanding how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico systems biology analyses support 5-MeO-DMT’s anti-inflammatory effects and reveal a modulation of proteins associated with long-term potentiation, the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.


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