Is DRM lipid composition relevant in cell-extracellular matrix adhesion structures?

Márquez, Marı́a Gabriela; Sterín-Speziale, Norma

doi:10.4161/cam.2.3.6604

Cited by 2 publications

(2 citation statements)

References 30 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…; Parton and Simons ). These structures are enriched in cholesterol and sphingolipids, and changes in the lipid composition are known to interfere with protein trafficking to the cell surface and cell adhesion (Marquez and Sterin‐Speziale ; Maalouf et al . ).…”

Section: Discussionmentioning

confidence: 99%

Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia

Testai

Kilkus

Berdyshev

et al. 2014

Journal of Neurochemistry

View full text Add to dashboard Cite

Hypoxia has been previously shown to inhibit the dihydroceramide (DHC) desaturase, leading to the accumulation of DHC. In this study, we used metabolic labeling with [3H]-palmitate, HPLC/MS/MS analysis, and specific inhibitors to show numerous sphingolipid changes after oxygen deprivation in cerebral microendothelial cells. The increased DHC, particularly long-chain forms, was observed in both whole cells and detergent-resistant membranes. This was reversed by reoxygenation and blocked by the de novo sphingolipid synthesis inhibitor myriocin, but not by the neutral sphingomyelinase inhibitor GW-4869. Furthermore, oxygen deprivation of microendothelial cells increased levels of dihydro-sphingosine (DH-Sph), DH-sphingosine1-phosphate (DH-S1P), DH-sphingomyelin (DH-SM), DH-glucosylceramide (DH-GlcCer), and S1P levels. In vitro assays revealed no changes in the activity of sphingomyelinases or sphingomyelin synthase, but resulted in reduced S1P lyase activity and 40% increase in glucosylceramide synthase (GCS) activity, which was reversed by reoxygenation. Inhibition of the de novo sphingolipid pathway (myriocin) or GCS (EtPoD4) induced endothelial barrier dysfunction and increased caspase 3-mediated cell death in response to hypoxia. Our findings suggest that hypoxia induces synthesis of S1P and multiple dihydrosphingolipids, including DHC, DH-SM, DH-GlcCer, DH-Sph and DH-S1P, which may be involved in ameliorating the effects of stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia

Testai

Kilkus

Berdyshev

et al. 2014

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…It is yet to be determined why ALK3 is more readily recruited to FAs than BMPRII upon BMP2 treatment. It has been reported that many of the molecular components that regulate cell–ECM adhesion are associated with cholesterol and sphingolipid-enriched detergent-resistant membrane (DRM) microdomains, which are also enriched in the acidic phospholipid PI(4,5)P2 ( Pande, 2000 ; Márquez and Sterin-Speziale, 2008 ). Lipid modifications, such as palmitoylation, enable molecules to partition into such locally generated specific microenvironments ( Lorent and Levental, 2015 ; Lorent et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Integrin-based adhesion compartmentalizes ALK3 of the BMPRII to control cell adhesion and migration

Guevara-Garcia

Fourel

Bourrin-Reynard

et al. 2022

Journal of Cell Biology

View full text Add to dashboard Cite

The spatial organization of cell-surface receptors is fundamental for the coordination of biological responses to physical and biochemical cues of the extracellular matrix. How serine/threonine kinase receptors, ALK3-BMPRII, cooperate with integrins upon BMP2 to drive cell migration is unknown. Whether the dynamics between integrins and BMP receptors intertwine in space and time to guide adhesive processes is yet to be elucidated. We found that BMP2 stimulation controls the spatial organization of BMPRs by segregating ALK3 from BMPRII into β3 integrin-containing focal adhesions. The selective recruitment of ALK3 to focal adhesions requires β3 integrin engagement and ALK3 activation. BMP2 controls the partitioning of immobilized ALK3 within and outside focal adhesions according to single-protein tracking and super-resolution imaging. The spatial control of ALK3 in focal adhesions by optogenetics indicates that ALK3 acts as an adhesive receptor by eliciting cell spreading required for cell migration. ALK3 segregation from BMPRII in integrin-based adhesions is a key aspect of the spatio-temporal control of BMPR signaling.

show abstract

Is DRM lipid composition relevant in cell-extracellular matrix adhesion structures?

Cited by 2 publications

References 30 publications

Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia

Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia

Integrin-based adhesion compartmentalizes ALK3 of the BMPRII to control cell adhesion and migration

Contact Info

Product

Resources

About