Profile of Carolina Barillas-Mury

Gabrielsen, Paul

doi:10.1073/pnas.1423225112

Cited by 3 publications

(8 citation statements)

References 14 publications

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“…[ 8 ]). For example, it has been proposed and confirmed experimentally that the ER tubules and sheets are sculptured by linear arrays of aligned arc-like scaffolds formed by oligomers of reticulons and DP1/Yop1 family proteins [ 57 – 59 ]. According to the results of the present work, formation of such arrays may be driven by the scaffold attractive and orientational interactions mediated by the membrane bending deformations.…”

Section: Discussionmentioning

confidence: 99%

Membrane-Mediated Interaction between Strongly Anisotropic Protein Scaffolds

Schweitzer

Kozlov

2015

PLoS Comput Biol

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Specialized proteins serve as scaffolds sculpting strongly curved membranes of intracellular organelles. Effective membrane shaping requires segregation of these proteins into domains and is, therefore, critically dependent on the protein-protein interaction. Interactions mediated by membrane elastic deformations have been extensively analyzed within approximations of large inter-protein distances, small extents of the protein-mediated membrane bending and small deviations of the protein shapes from isotropic spherical segments. At the same time, important classes of the realistic membrane-shaping proteins have strongly elongated shapes with large and highly anisotropic curvature. Here we investigated, computationally, the membrane mediated interaction between proteins or protein oligomers representing membrane scaffolds with strongly anisotropic curvature, and addressed, quantitatively, a specific case of the scaffold geometrical parameters characterizing BAR domains, which are crucial for membrane shaping in endocytosis. In addition to the previously analyzed contributions to the interaction, we considered a repulsive force stemming from the entropy of the scaffold orientation. We computed this interaction to be of the same order of magnitude as the well-known attractive force related to the entropy of membrane undulations. We demonstrated the scaffold shape anisotropy to cause a mutual aligning of the scaffolds and to generate a strong attractive interaction bringing the scaffolds close to each other to equilibrium distances much smaller than the scaffold size. We computed the energy of interaction between scaffolds of a realistic geometry to constitute tens of kBT, which guarantees a robust segregation of the scaffolds into domains.

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Section: Discussionmentioning

confidence: 99%

Membrane-Mediated Interaction between Strongly Anisotropic Protein Scaffolds

Schweitzer

Kozlov

2015

PLoS Comput Biol

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“…Pancreatic cancer cells [ 44 ] and even neural crest derived neuroblastoma cells [ 45 ] have shown sensitivity to zoledronic acid treatment. Very recently, zoledronic acid was proven to enhance the effect of EGFR-inhibitors and even to overcome resistance acquired through the gatekeeper mutation T790M in non-small cell lung cancer, breast cancer and colorectal cancer [ 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells

et al. 2015

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While targeted therapy brought a new era in the treatment of BRAF mutant melanoma, therapeutic options for non-BRAF mutant cases are still limited. In order to explore the antitumor activity of prenylation inhibition we investigated the response to zoledronic acid treatment in thirteen human melanoma cell lines with known BRAF, NRAS and PTEN mutational status. Effect of zoledronic acid on proliferation, clonogenic potential, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were investigated in vitro with SRB, TUNEL and PARP cleavage assays and videomicroscopy and immunoblot measurements, respectively. Subcutaneous and spleen-to-liver colonization xenograft mouse models were used to evaluate the influence of zoledronic acid treatment on primary and disseminated tumor growth of melanoma cells in vivo. Zoledronic acid more efficiently decreased short-term in vitro viability in NRAS mutant cells when compared to BRAF mutant and BRAF/NRAS wild-type cells. In line with this finding, following treatment decreased activation of ribosomal protein S6 was found in NRAS mutant cells. Zoledronic acid demonstrated no significant synergism in cell viability inhibition or apoptosis induction with cisplatin or DTIC treatment in vitro. Importantly, zoledronic acid could inhibit clonogenic growth in the majority of melanoma cell lines except in the three BRAF mutant but PTEN wild-type melanoma lines. A similar pattern was observed in apoptosis induction experiments. In vivo zoledronic acid did not inhibit the subcutaneous growth or spleen-to-liver colonization of melanoma cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. Nevertheless, we also demonstrated that therapeutic sensitivity might be influenced by the PTEN status of BRAF mutant melanoma cells. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target prenylation in melanoma cells.

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“…Solid-state nuclear magnetic resonance (NMR) measurements and filament mass per length determinations show that amyloid filaments of the prion domains (the amyloid-forming parts) of the yeast prion proteins Sup35p, Ure2p, and Rnq1p have a folded, in-register, parallel β-sheet architecture ( Fig. 1 ) (e.g., [ 15 , 16 ]). For Sup35p, we have evidence for the location of some folds [ 16 ].…”

Section: Structure Explains Inheritancementioning

confidence: 99%

“…1 ) (e.g., [ 15 , 16 ]). For Sup35p, we have evidence for the location of some folds [ 16 ]. This means that for each residue, there is a line of identical side chains along the long axis of the fiber.…”

Section: Structure Explains Inheritancementioning

confidence: 99%

“…Recently, we generated an array of [URE3]s in a btn2 Δ cur1 Δ strain, and found that nearly all such prion isolates were cured by restoration of just the normal levels of either Btn2p or Cur1p (although curing was most efficient if both were restored) [ 21 ]. Direct measurements showed that prion variants cured by normal levels of Btn2p or Cur1p had seed numbers several fold lower than variants that were only cured by overproduction of one or the other of these proteins [ 21 ]. These “ B tn2- C ur1-hyper s ensitive” variants ([URE3-bcs]) were somewhat unstable and often converted to variants only cured by overproduction of Btn2p or Cur1p.…”

Section: The Anti-prion Proteins Btn2 and Cur1mentioning

confidence: 99%

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