---
_id: '8988'
abstract:
- lang: eng
text: The differentiation of cells depends on a precise control of their internal
organization, which is the result of a complex dynamic interplay between the cytoskeleton,
molecular motors, signaling molecules, and membranes. For example, in the developing
neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP]
with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite
branching by regulating the small GTPase ARF6. Together with the motor protein
KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol
(3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity.
However, what defines the function of ADAP1 and how its different roles are coordinated
are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions.
We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well
as PI(3,4)P2 act as stop signals for this transport instead of being transported.
We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity
to catalyze GTP hydrolysis by ARF6. Together, our results support a model for
the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters
high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates
from the motor to inactivate ARF6, promoting dendrite branching.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: EM-Fac
acknowledgement: "We thank Urban Bezeljak, Natalia Baranova, Mar Lopez-Pelegrin, Catarina
Alcarva, and Victoria Faas for sharing reagents and helpful discussions. We thank
Veronika Szentirmai for help with protein purifications. We thank Carrie Bernecky,
Sascha Martens, and the M.L. lab for comments on the manuscript. We thank the bioimaging
facility, the life science facility, and Armel Nicolas from the mass spec facility
at the Institute of Science and Technology (IST) Austria for technical support.
C.D. acknowledges funding from the IST fellowship program; this work was supported
by Human Frontier Science Program Young Investigator Grant\r\nRGY0083/2016. "
article_number: e2010054118
article_processing_charge: No
article_type: original
author:
- first_name: Christian F
full_name: Düllberg, Christian F
id: 459064DC-F248-11E8-B48F-1D18A9856A87
last_name: Düllberg
orcid: 0000-0001-6335-9748
- first_name: Albert
full_name: Auer, Albert
id: 3018E8C2-F248-11E8-B48F-1D18A9856A87
last_name: Auer
orcid: 0000-0002-3580-2906
- first_name: Nikola
full_name: Canigova, Nikola
id: 3795523E-F248-11E8-B48F-1D18A9856A87
last_name: Canigova
orcid: 0000-0002-8518-5926
- first_name: Katrin
full_name: Loibl, Katrin
id: 3760F32C-F248-11E8-B48F-1D18A9856A87
last_name: Loibl
orcid: 0000-0002-2429-7668
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
citation:
ama: Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1. PNAS. 2021;118(1). doi:10.1073/pnas.2010054118
apa: Düllberg, C. F., Auer, A., Canigova, N., Loibl, K., & Loose, M. (2021).
In vitro reconstitution reveals phosphoinositides as cargo-release factors and
activators of the ARF6 GAP ADAP1. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2010054118
chicago: Düllberg, Christian F, Albert Auer, Nikola Canigova, Katrin Loibl, and
Martin Loose. “In Vitro Reconstitution Reveals Phosphoinositides as Cargo-Release
Factors and Activators of the ARF6 GAP ADAP1.” PNAS. National Academy of
Sciences, 2021. https://doi.org/10.1073/pnas.2010054118.
ieee: C. F. Düllberg, A. Auer, N. Canigova, K. Loibl, and M. Loose, “In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1,” PNAS, vol. 118, no. 1. National Academy of Sciences, 2021.
ista: Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. 2021. In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1. PNAS. 118(1), e2010054118.
mla: Düllberg, Christian F., et al. “In Vitro Reconstitution Reveals Phosphoinositides
as Cargo-Release Factors and Activators of the ARF6 GAP ADAP1.” PNAS, vol.
118, no. 1, e2010054118, National Academy of Sciences, 2021, doi:10.1073/pnas.2010054118.
short: C.F. Düllberg, A. Auer, N. Canigova, K. Loibl, M. Loose, PNAS 118 (2021).
date_created: 2021-01-03T23:01:23Z
date_published: 2021-01-05T00:00:00Z
date_updated: 2023-08-04T11:20:46Z
day: '05'
department:
- _id: MaLo
- _id: MiSi
doi: 10.1073/pnas.2010054118
external_id:
isi:
- '000607270100018'
pmid:
- '33443153'
intvolume: ' 118'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.2010054118
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2599F062-B435-11E9-9278-68D0E5697425
grant_number: RGY0083/2016
name: Reconstitution of cell polarity and axis determination in a cell-free system
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: In vitro reconstitution reveals phosphoinositides as cargo-release factors
and activators of the ARF6 GAP ADAP1
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 118
year: '2021'
...
---
_id: '8993'
abstract:
- lang: eng
text: N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar)
transport of the hormone auxin in plants. For decades, it has been a pivotal tool
in elucidating the unique polar auxin transport-based processes underlying plant
growth and development. Its exact mode of action has long been sought after and
is still being debated, with prevailing mechanistic schemes describing only indirect
connections between NPA and the main transporters responsible for directional
transport, namely PIN auxin exporters. Here we present data supporting a model
in which NPA associates with PINs in a more direct manner than hitherto postulated.
We show that NPA inhibits PIN activity in a heterologous oocyte system and that
expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to
specific saturable NPA binding. We thus propose that PINs are a bona fide NPA
target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent
auxin transport and a logical parsimonious explanation for the known physiological
effects of NPA on plant growth, as well as an alternative hypothesis to interpret
past and future results. We also introduce PIN dimerization and describe an effect
of NPA on this, suggesting that NPA binding could be exploited to gain insights
into structural aspects of PINs related to their transport mechanism.
acknowledgement: "This work was supported by Austrian Science Fund Grant FWF P21533-B20
(to L.A.); German Research Foundation Grant DFG HA3468/6-1 (to U.Z.H.); and European
Research Council Grant 742985 (to J.F.). We thank Herta Steinkellner and Alexandra
Castilho for N. benthamiana plants, Fabian Nagelreiter for statistical advice, Lanassa
Bassukas for help with [ɣ32P]-\r\nATP assays, and Josef Penninger for providing
access to mass spectrometry instruments at the Vienna BioCenter Core Facilities.
We thank PNAS reviewers for the many comments and suggestions that helped to improve
this manuscript."
article_number: e2020857118
article_processing_charge: No
article_type: original
author:
- first_name: Lindy
full_name: Abas, Lindy
last_name: Abas
- first_name: Martina
full_name: Kolb, Martina
last_name: Kolb
- first_name: Johannes
full_name: Stadlmann, Johannes
last_name: Stadlmann
- first_name: Dorina P.
full_name: Janacek, Dorina P.
last_name: Janacek
- first_name: Kristina
full_name: Lukic, Kristina
id: 2B04DB84-F248-11E8-B48F-1D18A9856A87
last_name: Lukic
orcid: 0000-0003-1581-881X
- first_name: Claus
full_name: Schwechheimer, Claus
last_name: Schwechheimer
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Lukas
full_name: Mach, Lukas
last_name: Mach
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
- first_name: Ulrich Z.
full_name: Hammes, Ulrich Z.
last_name: Hammes
citation:
ama: Abas L, Kolb M, Stadlmann J, et al. Naphthylphthalamic acid associates with
and inhibits PIN auxin transporters. PNAS. 2021;118(1). doi:10.1073/pnas.2020857118
apa: Abas, L., Kolb, M., Stadlmann, J., Janacek, D. P., Lukic, K., Schwechheimer,
C., … Hammes, U. Z. (2021). Naphthylphthalamic acid associates with and inhibits
PIN auxin transporters. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2020857118
chicago: Abas, Lindy, Martina Kolb, Johannes Stadlmann, Dorina P. Janacek, Kristina
Lukic, Claus Schwechheimer, Leonid A Sazanov, Lukas Mach, Jiří Friml, and Ulrich
Z. Hammes. “Naphthylphthalamic Acid Associates with and Inhibits PIN Auxin Transporters.”
PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2020857118.
ieee: L. Abas et al., “Naphthylphthalamic acid associates with and inhibits
PIN auxin transporters,” PNAS, vol. 118, no. 1. National Academy of Sciences,
2021.
ista: Abas L, Kolb M, Stadlmann J, Janacek DP, Lukic K, Schwechheimer C, Sazanov
LA, Mach L, Friml J, Hammes UZ. 2021. Naphthylphthalamic acid associates with
and inhibits PIN auxin transporters. PNAS. 118(1), e2020857118.
mla: Abas, Lindy, et al. “Naphthylphthalamic Acid Associates with and Inhibits PIN
Auxin Transporters.” PNAS, vol. 118, no. 1, e2020857118, National Academy
of Sciences, 2021, doi:10.1073/pnas.2020857118.
short: L. Abas, M. Kolb, J. Stadlmann, D.P. Janacek, K. Lukic, C. Schwechheimer,
L.A. Sazanov, L. Mach, J. Friml, U.Z. Hammes, PNAS 118 (2021).
date_created: 2021-01-03T23:01:23Z
date_published: 2021-01-05T00:00:00Z
date_updated: 2023-08-07T13:29:23Z
day: '05'
department:
- _id: JiFr
- _id: LeSa
doi: 10.1073/pnas.2020857118
ec_funded: 1
external_id:
isi:
- '000607270100073'
pmid:
- '33443187'
intvolume: ' 118'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.2020857118
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1073/pnas.2102232118
scopus_import: '1'
status: public
title: Naphthylphthalamic acid associates with and inhibits PIN auxin transporters
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 118
year: '2021'
...
---
_id: '8698'
abstract:
- lang: eng
text: The brain represents and reasons probabilistically about complex stimuli and
motor actions using a noisy, spike-based neural code. A key building block for
such neural computations, as well as the basis for supervised and unsupervised
learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional
neural activity patterns. Despite progress in statistical modeling of neural responses
and deep learning, current approaches either do not scale to large neural populations
or cannot be implemented using biologically realistic mechanisms. Inspired by
the sparse and random connectivity of real neuronal circuits, we present a model
for neural codes that accurately estimates the likelihood of individual spiking
patterns and has a straightforward, scalable, efficient, learnable, and realistic
neural implementation. This model’s performance on simultaneously recorded spiking
activity of >100 neurons in the monkey visual and prefrontal cortices is comparable
with or better than that of state-of-the-art models. Importantly, the model can
be learned using a small number of samples and using a local learning rule that
utilizes noise intrinsic to neural circuits. Slower, structural changes in random
connectivity, consistent with rewiring and pruning processes, further improve
the efficiency and sparseness of the resulting neural representations. Our results
merge insights from neuroanatomy, machine learning, and theoretical neuroscience
to suggest random sparse connectivity as a key design principle for neuronal computation.
acknowledgement: We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir
Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn
for invaluable discussions of the learning rule. This work was supported by European
Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12
(to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs.
Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to
R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration
on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative
Research in Computational Neuroscience) grant (to R.K. and E.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Ori
full_name: Maoz, Ori
last_name: Maoz
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mohamad Saleh
full_name: Esteki, Mohamad Saleh
last_name: Esteki
- first_name: Roozbeh
full_name: Kiani, Roozbeh
last_name: Kiani
- first_name: Elad
full_name: Schneidman, Elad
last_name: Schneidman
citation:
ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the
National Academy of Sciences of the United States of America. 2020;117(40):25066-25073.
doi:10.1073/pnas.1912804117
apa: Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., & Schneidman, E. (2020).
Learning probabilistic neural representations with randomly connected circuits.
Proceedings of the National Academy of Sciences of the United States of America.
National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117
chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad
Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected
Circuits.” Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117.
ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic
neural representations with randomly connected circuits,” Proceedings of the
National Academy of Sciences of the United States of America, vol. 117, no.
40. National Academy of Sciences, pp. 25066–25073, 2020.
ista: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the National
Academy of Sciences of the United States of America. 117(40), 25066–25073.
mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly
Connected Circuits.” Proceedings of the National Academy of Sciences of the
United States of America, vol. 117, no. 40, National Academy of Sciences,
2020, pp. 25066–73, doi:10.1073/pnas.1912804117.
short: O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of
the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.
date_created: 2020-10-25T23:01:16Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:23Z
day: '06'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.1912804117
external_id:
isi:
- '000579045200012'
pmid:
- '32948691'
file:
- access_level: open_access
checksum: c6a24fdecf3f28faf447078e7a274a88
content_type: application/pdf
creator: cziletti
date_created: 2020-10-27T14:57:50Z
date_updated: 2020-10-27T14:57:50Z
file_id: '8713'
file_name: 2020_PNAS_Maoz.pdf
file_size: 1755359
relation: main_file
success: 1
file_date_updated: 2020-10-27T14:57:50Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '40'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '10'
oa: 1
oa_version: Published Version
page: 25066-25073
pmid: 1
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Learning probabilistic neural representations with randomly connected circuits
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
---
_id: '8699'
abstract:
- lang: eng
text: In the high spin–orbit-coupled Sr2IrO4, the high sensitivity of the ground
state to the details of the local lattice structure shows a large potential for
the manipulation of the functional properties by inducing local lattice distortions.
We use epitaxial strain to modify the Ir–O bond geometry in Sr2IrO4 and perform
momentum-dependent resonant inelastic X-ray scattering (RIXS) at the metal and
at the ligand sites to unveil the response of the low-energy elementary excitations.
We observe that the pseudospin-wave dispersion for tensile-strained Sr2IrO4 films
displays large softening along the [h,0] direction, while along the [h,h] direction
it shows hardening. This evolution reveals a renormalization of the magnetic interactions
caused by a strain-driven cross-over from anisotropic to isotropic interactions
between the magnetic moments. Moreover, we detect dispersive electron–hole pair
excitations which shift to lower (higher) energies upon compressive (tensile)
strain, manifesting a reduction (increase) in the size of the charge gap. This
behavior shows an intimate coupling between charge excitations and lattice distortions
in Sr2IrO4, originating from the modified hopping elements between the t2g orbitals.
Our work highlights the central role played by the lattice degrees of freedom
in determining both the pseudospin and charge excitations of Sr2IrO4 and provides
valuable information toward the control of the ground state of complex oxides
in the presence of high spin–orbit coupling.
acknowledgement: 'We gratefully acknowledge C. Sahle for experimental support at the
ID20 beamline of the ESRF. The soft X-ray experiments were carried out at the ADRESS
beamline of the Swiss Light Source, Paul Scherrer Institut (PSI). E. Paris and T.S.
thank X. Lu and C. Monney for valuable discussions. The work at PSI is supported
by the Swiss National Science Foundation (SNSF) through Project 200021_178867, the
NCCR (National Centre of Competence in Research) MARVEL (Materials’ Revolution:
Computational Design and Discovery of Novel Materials) and the Sinergia network
Mott Physics Beyond the Heisenberg Model (MPBH) (SNSF Research Grants CRSII2_160765/1
and CRSII2_141962). K.W. acknowledges support by the Narodowe Centrum Nauki Projects
2016/22/E/ST3/00560 and 2016/23/B/ST3/00839. E.M.P. and M.N. acknowledge funding
from the European Union’s Horizon 2020 research and innovation programme under the
Marie Sklodowska-Curie Grant Agreements 754411 and 701647, respectively. M.R. was
supported by the Swiss National Science Foundation under Project 200021 – 182695.
This research used resources of the APS, a U.S. Department of Energy (DOE) Office
of Science User Facility operated for the DOE Office of Science by Argonne National
Laboratory under Contract DE-AC02-06CH11357.'
article_processing_charge: No
article_type: original
author:
- first_name: Eugenio
full_name: Paris, Eugenio
last_name: Paris
- first_name: Yi
full_name: Tseng, Yi
last_name: Tseng
- first_name: Ekaterina
full_name: Paerschke, Ekaterina
id: 8275014E-6063-11E9-9B7F-6338E6697425
last_name: Paerschke
orcid: 0000-0003-0853-8182
- first_name: Wenliang
full_name: Zhang, Wenliang
last_name: Zhang
- first_name: Mary H
full_name: Upton, Mary H
last_name: Upton
- first_name: Anna
full_name: Efimenko, Anna
last_name: Efimenko
- first_name: Katharina
full_name: Rolfs, Katharina
last_name: Rolfs
- first_name: Daniel E
full_name: McNally, Daniel E
last_name: McNally
- first_name: Laura
full_name: Maurel, Laura
last_name: Maurel
- first_name: Muntaser
full_name: Naamneh, Muntaser
last_name: Naamneh
- first_name: Marco
full_name: Caputo, Marco
last_name: Caputo
- first_name: Vladimir N
full_name: Strocov, Vladimir N
last_name: Strocov
- first_name: Zhiming
full_name: Wang, Zhiming
last_name: Wang
- first_name: Diego
full_name: Casa, Diego
last_name: Casa
- first_name: Christof W
full_name: Schneider, Christof W
last_name: Schneider
- first_name: Ekaterina
full_name: Pomjakushina, Ekaterina
last_name: Pomjakushina
- first_name: Krzysztof
full_name: Wohlfeld, Krzysztof
last_name: Wohlfeld
- first_name: Milan
full_name: Radovic, Milan
last_name: Radovic
- first_name: Thorsten
full_name: Schmitt, Thorsten
last_name: Schmitt
citation:
ama: Paris E, Tseng Y, Paerschke E, et al. Strain engineering of the charge and
spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of
Sciences of the United States of America. 2020;117(40):24764-24770. doi:10.1073/pnas.2012043117
apa: Paris, E., Tseng, Y., Paerschke, E., Zhang, W., Upton, M. H., Efimenko, A.,
… Schmitt, T. (2020). Strain engineering of the charge and spin-orbital interactions
in Sr2IrO4. Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2012043117
chicago: Paris, Eugenio, Yi Tseng, Ekaterina Paerschke, Wenliang Zhang, Mary H Upton,
Anna Efimenko, Katharina Rolfs, et al. “Strain Engineering of the Charge and Spin-Orbital
Interactions in Sr2IrO4.” Proceedings of the National Academy of Sciences of
the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2012043117.
ieee: E. Paris et al., “Strain engineering of the charge and spin-orbital
interactions in Sr2IrO4,” Proceedings of the National Academy of Sciences of
the United States of America, vol. 117, no. 40. National Academy of Sciences,
pp. 24764–24770, 2020.
ista: Paris E, Tseng Y, Paerschke E, Zhang W, Upton MH, Efimenko A, Rolfs K, McNally
DE, Maurel L, Naamneh M, Caputo M, Strocov VN, Wang Z, Casa D, Schneider CW, Pomjakushina
E, Wohlfeld K, Radovic M, Schmitt T. 2020. Strain engineering of the charge and
spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of Sciences
of the United States of America. 117(40), 24764–24770.
mla: Paris, Eugenio, et al. “Strain Engineering of the Charge and Spin-Orbital Interactions
in Sr2IrO4.” Proceedings of the National Academy of Sciences of the United
States of America, vol. 117, no. 40, National Academy of Sciences, 2020, pp.
24764–70, doi:10.1073/pnas.2012043117.
short: E. Paris, Y. Tseng, E. Paerschke, W. Zhang, M.H. Upton, A. Efimenko, K. Rolfs,
D.E. McNally, L. Maurel, M. Naamneh, M. Caputo, V.N. Strocov, Z. Wang, D. Casa,
C.W. Schneider, E. Pomjakushina, K. Wohlfeld, M. Radovic, T. Schmitt, Proceedings
of the National Academy of Sciences of the United States of America 117 (2020)
24764–24770.
date_created: 2020-10-25T23:01:17Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:52Z
day: '06'
ddc:
- '530'
department:
- _id: MiLe
doi: 10.1073/pnas.2012043117
ec_funded: 1
external_id:
arxiv:
- '2009.12262'
isi:
- '000579059100029'
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page: 24764-24770
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project:
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call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Strain engineering of the charge and spin-orbital interactions in Sr2IrO4
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image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
---
_id: '9000'
abstract:
- lang: eng
text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
quantitative mapping from promoter sequences to gene-expression levels that is
compatible with in vivo and in vitro biophysical measurements. Such concordance
has not been achieved for models of enhancer function in eukaryotes. In equilibrium
models, it is difficult to reconcile the reported short transcription factor (TF)
residence times on the DNA with the high specificity of regulation. In nonequilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal nonequilibrium enhancer
models that yield desired regulatory phenotypes: low TF residence time, high specificity,
and tunable cooperativity. We find that a single extra parameter, interpretable
as the “linking rate,” by which bound TFs interact with Mediator components, enables
our models to escape equilibrium bounds and access optimal regulatory phenotypes,
while remaining consistent with the reported phenomenology and simple enough to
be inferred from upcoming experiments. We further find that high specificity in
nonequilibrium models is in a trade-off with gene-expression noise, predicting
bursty dynamics—an experimentally observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space of nonequilibrium enhancer models
to a much smaller subspace that optimally realizes biological function, we deliver
a rich class of models that could be tractably inferred from data in the near
future.'
acknowledgement: G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018.
R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks
S. Avvakumov for helpful discussions.
article_processing_charge: No
article_type: original
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function.
PNAS. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal
enhancer function. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of
Optimal Enhancer Function.” PNAS. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer
function,” PNAS, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622,
2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer
function. PNAS. 117(50), 31614–31622.
mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS,
vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117.
short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622.
date_created: 2021-01-10T23:01:17Z
date_published: 2020-12-15T00:00:00Z
date_updated: 2023-08-24T11:10:22Z
day: '15'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.2006731117
external_id:
isi:
- '000600608300015'
pmid:
- '33268497'
file:
- access_level: open_access
checksum: 69039cd402a571983aa6cb4815ffa863
content_type: application/pdf
creator: dernst
date_created: 2021-01-11T08:37:31Z
date_updated: 2021-01-11T08:37:31Z
file_id: '9004'
file_name: 2020_PNAS_Grah.pdf
file_size: 1199247
relation: main_file
success: 1
file_date_updated: 2021-01-11T08:37:31Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '50'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 31614-31622
pmid: 1
project:
- _id: 2665AAFE-B435-11E9-9278-68D0E5697425
grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/
scopus_import: '1'
status: public
title: Nonequilibrium models of optimal enhancer function
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...