The HumanSerum Deprivation ResponseGene (SDPR) Maps to 2q32–q33 and Codes for a Phosphatidylserine-Binding Protein

Gustincich, Stefano; Vatta, Paolo; Goruppi, Sandro; Wolf, Marlene; Saccone, Salvatore; Valle, Giuliano Della; Baggiolini, Marco; Schneider, Claudio

doi:10.1006/geno.1998.5733

Cited by 66 publications

(59 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is consistent with cavin1 being the PtdSer-sensitive component needed for proper function or stabilization. The polybasic sites of cavin1, HR1 and HR2 domains, were proposed to bind anionic phospholipids, including PtdSer through charge-based interactions (16,17,20,55). In support of this notion, we find that chronic depletion of the majority (Ϸ80%) of PtdSer limits the ability of cavin1 to associate with Cav1 and the PM.…”

Section: Phosphatidylserine Is Required To Support the Formation Of Csupporting

confidence: 66%

“…The cavin family consists of four members, cavin1 to cavin4, that are required to stabilize the Cav1 proteins and to shape caveolae (16 -19). The cavins also have the ability to bind to PtdSer (16,17,20). Furthermore, a recent study demonstrated that there are 50 cavin1 molecules per caveola (15,21).…”

Section: Edited By Dennis R Voelkermentioning

confidence: 99%

“…Both Cav and cavin proteins bind to PtdSer in vitro, and this binding is postulated to be necessary for the function and assembly of caveolae in vivo (13,14,17,20). To complement the experiments investigating the localization and dynamics of Cav1-GFP, we generated a cavin1-GFP stably expressing HeLa cells (HeLa/cavin1-GFP) to monitor cavin1 localization following perturbation of PtdSer.…”

Section: Sequestering Plasmalemmal Ptdser Interferes With Caveolar Asmentioning

confidence: 99%

See 2 more Smart Citations

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Hirama

Das

Yang

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Dennis R. VoelkerCaveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in cholesterol and sphingolipids. They have many physiological functions, including endocytic transport, mechanosensing, and regulation of membrane and lipid transport. Caveola formation relies on integral membrane proteins termed caveolins (Cavs) and the cavin family of peripheral proteins. Both protein families bind anionic phospholipids, but the precise roles of these lipids are unknown. Here, we studied the effects of phosphatidylserine (PtdSer), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) on caveolar formation and dynamics. Using live-cell, single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we compared the effect of PtdSer disruption or phosphoinositide depletion with caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial role in both caveola formation and stability. Sequestration or depletion of PtdSer decreased the number of detectable Cav1-GFP puncta and the number of caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was increased. Using rapamycin-recruitable phosphatases, we also found that the acute depletion of PtdIns4P and PtdIns (4,5)P 2 has minimal impact on caveola assembly but results in decreased lateral confinement. Finally, we show in a model of phospholipid scrambling, a feature of apoptotic cells, that caveola stability is acutely affected by the scrambling. We conclude that the predominant plasmalemmal anionic lipid PtdSer is essential for proper Cav clustering, caveola formation, and caveola dynamics and that membrane scrambling can perturb caveolar stability.

show abstract

Section: Phosphatidylserine Is Required To Support the Formation Of Csupporting

confidence: 66%

Section: Edited By Dennis R Voelkermentioning

confidence: 99%

Section: Sequestering Plasmalemmal Ptdser Interferes With Caveolar Asmentioning

confidence: 99%

See 1 more Smart Citation

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Hirama

Das

Yang

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Cavins have been shown to bind to and/or recruit PKCα (Gustincich et al, 1999;Hill et al, 2012;Izumi et al, 1997), and cavin-1 knockdown results in increased caveolar mobility (Hill et al, 2008). Furthermore, cavin-1 is known to interact with EHD2 (Moren et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C (PKC)-mediated phosphorylation of PACSIN2 triggers the removal of caveolae from the plasma membrane

Senju

Rosenbaum

Shah

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

PACSIN2, a membrane-sculpting BAR domain protein, localizes to caveolae. Here, we found that protein kinase C (PKC) phosphorylates PACSIN2 at serine 313, thereby decreasing its membrane binding and tubulation capacities. Concomitantly, phosphorylation decreased the time span for which caveolae could be tracked at the plasma membrane (the 'tracking duration'). Analyses of the phospho-mimetic S313E mutant suggested that PACSIN2 phosphorylation was sufficient to reduce caveolartracking durations. Both hypotonic treatment and isotonic druginduced PKC activation increased PACSIN2 phosphorylation at serine 313 and shortened caveolar-tracking durations. Caveolartracking durations were also reduced upon the expression of other membrane-binding-deficient PACSIN2 mutants or upon RNA interference (RNAi)-mediated PACSIN2 depletion, pointing to a role for PACSIN2 levels in modulating the lifetime of caveolae. Interestingly, the decrease in membrane-bound PACSIN2 was inversely correlated with the recruitment and activity of dynamin 2, a GTPase that mediates membrane scission. Furthermore, expression of EHD2, which stabilizes caveolae and binds to PACSIN2, restored the tracking durations of cells with reduced PACSIN2 levels. These findings suggest that the PACSIN2 phosphorylation decreases its membrane-binding activity, thereby decreasing its stabilizing effect on caveolae and triggering dynaminmediated removal of caveolae.

show abstract

“…[38] Cavin2 was purified as a phosphatidylserine (PS)-binding protein and its messenger RNA (mRNA) is increased in a serum-deprived microenvironment. [39,40] Cavin2 is localized in the caveolae and binds PKC alpha. [41] The downregulation of Cavin2 induced the loss of Cav1 and Cavin1 expression and limited caveolae formation.…”

Section: The Caveolae Structurementioning

confidence: 99%

Caveolae and cancer: A new mechanical perspective

Lamaze¹,

Torrino²

2015

Biomed J

View full text Add to dashboard Cite

The HumanSerum Deprivation ResponseGene (SDPR) Maps to 2q32–q33 and Codes for a Phosphatidylserine-Binding Protein

Cited by 66 publications

References 42 publications

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Protein kinase C (PKC)-mediated phosphorylation of PACSIN2 triggers the removal of caveolae from the plasma membrane

Caveolae and cancer: A new mechanical perspective

Contact Info

Product

Resources

About