Evolution of programmed cell fusion: Common mechanisms and distinct functions

Oren‐Suissa, Meital; Podbilewicz, Benjamin

doi:10.1002/dvdy.22284

Cited by 33 publications

(19 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result of membrane contact, the outer phospholipid bilayers may provoke a transient fusion called hemifusion. Subsequently, the two membranes might locally form fusion pores or activation of fusogenic proteins leading to complete cell-cell fusion (21,22).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

Lehmann

Filipiak

Juzwa

et al. 2013

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Degeneration of the intervertebral disc (IVD) is the main cause of age-related damage of spinal tissues. Using multipotent mesenchymal stromal cells (MSCs) regenerative medicine intends to restore the IVD components of annulus fibrosus (AF) and nucleus pulposus (NP). In the present study NP cells (NPCs) and MSCs obtained from adolescent patients suffering from scoliosis were used. IVDs and vertebrae were obtained during surgery and subsequently processed in order to establish cultures of NPCs and MSCs. The two cell types were co-cultured in 1-µm pore size insert system (indirect co-culture) or on one surface (direct co-culture). Prior to co-culture in these systems one of the cell types was stained by lipophilic fluorescent dye DiD (red). The results demonstrated that regardless of the cell type, the flow of DiD from stained to non-stained cells was more efficient in the direct co-culture in comparison with the insert system. Moreover, in the direct system the DiD flow was more efficient from MSCs towards NPCs compared with that in the opposite direction. These data indicated that the membrane interchange between the two cell types was asymmetric. To discriminate the subpopulation of cells that underwent membrane interchange, cells were double stained with DiD and DiO (green). In the first part of the experiment NPCs were stained by DiO and MSCs by DiD. In the second, NPCs were stained by DiD and MSCs by DiO. The cells were co-cultured in the direct system for 8 days and subsequently analyzed by flow cytometry and confocal microscopy.This analysis revealed that >50% of cells were stained by the DiO and DiD dyes. NPCs and MSCs formed structures similar to tunnelling nanotubes (TnT). In conclusion, the formation of TnT-like structures is able to promote, phenotypic changes during the direct co-culture of NPCs with MSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

“…These approaches have a default assumption that MSCs 'learn' their phenotype from NPCs, and promote cell division in NPCs. However, the manner in which the NP phenotype can be mimicked by MSCs and whether or not this method is safe with regard to possible chromosomal rearrangement due to hybrid formation remain to be determined (22).…”

Section: Discussionmentioning

confidence: 99%

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

Lehmann

Filipiak

Juzwa

et al. 2013

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…In addition to C. elegans, seamless tubules are also found in the Drosophila tracheal system (13,14), and endothelial cell capillaries in zebrafish (15,16) and mammalian tissues (17,18). While there are various mechanisms proposed for the formation of seamless capillaries in zebrafish (15,16), the mechanism underlying the formation of mammalian seamless capillaries remains unclear (19,20). Interestingly, we found that human microvascular endothelial cells were also capable of self-contact-induced membrane fusion (Fig.…”

Section: Discussionmentioning

confidence: 84%

Self-contact elimination by membrane fusion

Sumida

Yamada

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mutual, homophilic cell-cell adhesion between epithelial cells is required for proper maintenance of epithelial barrier function. Whereas opposing membranes from neighboring cells rapidly assemble junctional complexes, self-contacting membranes curiously do not, suggesting that cells have the ability to prevent the maturation of self-junctions. Using a self-contact-inducing microfabricated substrate, we show that self-contacts of normal epithelial cells are rapidly eliminated by membrane fusion between two opposing plasma membranes of a single cell. This membrane fusion is most frequently observed in E-cadherin-expressing epithelial cells, but not in fibroblasts. The efficiency of self-contact elimination depends on extracellular calcium concentration and the level of E-cadherin, suggesting that E-cadherin, although not required, enhances membrane fusion efficiency by bringing opposing membranes into close apposition to one another. Additionally, Rho-associated protein kinase inhibition decreases self-contact-induced membrane fusion of epithelial cells, suggesting that this fusion may be mechanically regulated through the actin-myosin network. This self-contact-induced membrane fusion is a key elimination mechanism for unwanted self-junctions and may be a feature of cell self-recognition.seamless tubule | contractility | soft lithography T he formation of intimate cell-cell adhesion is the first critical step in the development of multicellular organisms. Many cell types, particularly epithelial cells, form and maintain cellcell junctions with neighboring cells through homophilic interactions of cell adhesion proteins. When the plasma membranes of neighboring cells physically interact, cell-cell adhesion proteins engage and autonomously and rapidly develop into mature cell junctions. Interestingly, in native environments, epithelial cells extend thin finger-like protrusions along the basal-lateral surface (1, 2). These flexible membrane extensions are capable of touching different regions of their own membrane surface, yet, mature cell junctional complexes have not been observed at self-contacts. The curious absence of cell junctions at selfcontacts suggests that cells are able to either prevent the autonomous assembly of self-junctions or rapidly eliminate nascent self-junctions.The fate of self-contacts is not entirely clear. During neuronal network formation, thin flexible neurites recognize self-contacts through homophilic interactions of surface receptors and repel one another, whereas heterophilic interactions between neighboring cells are more favorable (3,4). This type of self-avoidance is based on surface chemistry defined by the receptors on plasma membrane. Other adhesive cells that rely on homophilic interactions of adhesion proteins need an alternative strategy to avoid or eliminate self-contacts.Such a self-recognition pathway is essential as many other cell types have the capacity to generate self-contacts. For example, dynamic lamellipodia and membrane ruffles often fold onto adjacent membrane re...

show abstract

“…The fusion of mammalian cells into large syncytia is a well controlled process that is restricted to a limited set of cells, including gametes, macrophages, myoblasts, and trophoblasts [39,40]. Steinberg et al [38] demonstrated that the FGFRL1 receptor, when overexpressed, was capable of fusing CHO cells into multinucleated syncytia comprising several hundred nuclei.…”

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

Biology of FGFRL1, the fifth fibroblast growth factor receptor

Trüeb

2010

Cell. Mol. Life Sci.

120

102

View full text Add to dashboard Cite

FGFRL1 (fibroblast growth factor receptor like 1) is the most recently discovered member of the FGFR family. It contains three extracellular Ig-like domains similar to the classical FGFRs, but it lacks the protein tyrosine kinase domain and instead contains a short intracellular tail with a peculiar histidine-rich motif. The gene for FGFRL1 is found in all metazoans from sea anemone to mammals. FGFRL1 binds to FGF ligands and heparin with high affinity. It exerts a negative effect on cell proliferation, but a positive effect on cell differentiation. Mice with a targeted deletion of the Fgfrl1 gene die perinatally due to alterations in their diaphragm. These mice also show bilateral kidney agenesis, suggesting an essential role for Fgfrl1 in kidney development. A human patient with a frameshift mutation exhibits craniosynostosis, arguing for an additional role of FGFRL1 during bone formation. FGFRL1 contributes to the complexity of the FGF signaling system.

show abstract

Evolution of programmed cell fusion: Common mechanisms and distinct functions

Cited by 33 publications

References 160 publications

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

Self-contact elimination by membrane fusion

Biology of FGFRL1, the fifth fibroblast growth factor receptor

Contact Info

Product

Resources

About