---
_id: '11160'
abstract:
- lang: eng
text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
with an accelerated and delayed generation of, respectively, inhibitory and excitatory
neurons that yields, at days 60 and 120, symmetrically opposite expansions in
their proportions. This imbalance is consistent with an enlargement of cerebral
organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
CHD8-dependent molecular defects related to an abnormal program of proliferation
and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
our study uncovers reproducible developmental alterations that may be employed
for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
work supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
full_name: Villa, Carlo Emanuele
last_name: Villa
- first_name: Cristina
full_name: Cheroni, Cristina
last_name: Cheroni
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Alejandro
full_name: López-Tóbon, Alejandro
last_name: López-Tóbon
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Aysan Çerağ
full_name: Yahya, Aysan Çerağ
id: 365A65F8-F248-11E8-B48F-1D18A9856A87
last_name: Yahya
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Michele
full_name: Gabriele, Michele
last_name: Gabriele
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Mariano
full_name: Gabitto, Mariano
last_name: Gabitto
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Giuseppe
full_name: Testa, Giuseppe
last_name: Testa
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
to transient alterations in excitatory and inhibitory trajectories. Cell Reports.
2022;39(1). doi:10.1016/j.celrep.2022.110615
apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615
chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.
ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient
alterations in excitatory and inhibitory trajectories,” Cell Reports, vol.
39, no. 1. Elsevier, 2022.
ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol.
39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.
short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2024-03-28T23:30:45Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
isi:
- '000785983900003'
pmid:
- '35385734'
file:
- access_level: open_access
checksum: b4e8d68f0268dec499af333e6fd5d8e1
content_type: application/pdf
creator: dernst
date_created: 2022-04-15T09:06:25Z
date_updated: 2022-04-15T09:06:25Z
file_id: '11164'
file_name: 2022_CellReports_Villa.pdf
file_size: '7808644'
relation: main_file
success: 1
file_date_updated: 2022-04-15T09:06:25Z
has_accepted_license: '1'
intvolume: ' 39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication: Cell Reports
publication_identifier:
issn:
- 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12364'
relation: dissertation_contains
status: public
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
and inhibitory trajectories
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '546'
abstract:
- lang: eng
text: The precise control of neural stem cell (NSC) proliferation and differentiation
is crucial for the development and function of the human brain. Here, we review
the emerging links between the alteration of embryonic and adult neurogenesis
and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum
disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based
modeling and the novel therapeutic targets derived from these studies.
article_processing_charge: No
author:
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders.
Current Opinion in Neurobiology. 2018;48(2):131-138. doi:10.1016/j.conb.2017.12.005
apa: Sacco, R., Cacci, E., & Novarino, G. (2018). Neural stem cells in neuropsychiatric
disorders. Current Opinion in Neurobiology. Elsevier. https://doi.org/10.1016/j.conb.2017.12.005
chicago: Sacco, Roberto, Emanuele Cacci, and Gaia Novarino. “Neural Stem Cells in
Neuropsychiatric Disorders.” Current Opinion in Neurobiology. Elsevier,
2018. https://doi.org/10.1016/j.conb.2017.12.005.
ieee: R. Sacco, E. Cacci, and G. Novarino, “Neural stem cells in neuropsychiatric
disorders,” Current Opinion in Neurobiology, vol. 48, no. 2. Elsevier,
pp. 131–138, 2018.
ista: Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric
disorders. Current Opinion in Neurobiology. 48(2), 131–138.
mla: Sacco, Roberto, et al. “Neural Stem Cells in Neuropsychiatric Disorders.” Current
Opinion in Neurobiology, vol. 48, no. 2, Elsevier, 2018, pp. 131–38, doi:10.1016/j.conb.2017.12.005.
short: R. Sacco, E. Cacci, G. Novarino, Current Opinion in Neurobiology 48 (2018)
131–138.
date_created: 2018-12-11T11:47:06Z
date_published: 2018-02-01T00:00:00Z
date_updated: 2023-09-13T09:01:56Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.conb.2017.12.005
external_id:
isi:
- '000427101600018'
intvolume: ' 48'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa_version: None
page: 131 - 138
publication: Current Opinion in Neurobiology
publication_status: published
publisher: Elsevier
publist_id: '7268'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neural stem cells in neuropsychiatric disorders
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 48
year: '2018'
...
---
_id: '540'
abstract:
- lang: eng
text: RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of
RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis
virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection.
A major genetic determinant for its ability to persist maps to a single amino
acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional
consequences remain elusive. To unravel the L protein interactions with the host
proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics.
A subsequent mass-spectrometric analysis of L protein pulldowns from infected
human cells revealed a comprehensive network of interacting host proteins. The
obtained LCMV L protein interactome was bioinformatically integrated with known
host protein interactors of RdRps from other RNA viruses, emphasizing interconnected
modules of human proteins. Functional characterization of selected interactors
highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors.
To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired
virus control in chronic infection. These results provide insights into the complex
interactions of the arenavirus LCMV and other viral RdRps with the host proteome
and contribute to a better molecular understanding of how chronic viruses interact
with their host.
article_number: e1006758
author:
- first_name: Kseniya
full_name: Khamina, Kseniya
last_name: Khamina
- first_name: Alexander
full_name: Lercher, Alexander
last_name: Lercher
- first_name: Michael
full_name: Caldera, Michael
last_name: Caldera
- first_name: Christopher
full_name: Schliehe, Christopher
last_name: Schliehe
- first_name: Bojan
full_name: Vilagos, Bojan
last_name: Vilagos
- first_name: Mehmet
full_name: Sahin, Mehmet
last_name: Sahin
- first_name: Lindsay
full_name: Kosack, Lindsay
last_name: Kosack
- first_name: Anannya
full_name: Bhattacharya, Anannya
last_name: Bhattacharya
- first_name: Peter
full_name: Májek, Peter
last_name: Májek
- first_name: Alexey
full_name: Stukalov, Alexey
last_name: Stukalov
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Leo
full_name: James, Leo
last_name: James
- first_name: Daniel
full_name: Pinschewer, Daniel
last_name: Pinschewer
- first_name: Keiryn
full_name: Bennett, Keiryn
last_name: Bennett
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Andreas
full_name: Bergthaler, Andreas
last_name: Bergthaler
citation:
ama: Khamina K, Lercher A, Caldera M, et al. Characterization of host proteins interacting
with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens.
2017;13(12). doi:10.1371/journal.ppat.1006758
apa: Khamina, K., Lercher, A., Caldera, M., Schliehe, C., Vilagos, B., Sahin, M.,
… Bergthaler, A. (2017). Characterization of host proteins interacting with the
lymphocytic choriomeningitis virus L protein. PLoS Pathogens. Public Library
of Science. https://doi.org/10.1371/journal.ppat.1006758
chicago: Khamina, Kseniya, Alexander Lercher, Michael Caldera, Christopher Schliehe,
Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, et al. “Characterization of Host
Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS
Pathogens. Public Library of Science, 2017. https://doi.org/10.1371/journal.ppat.1006758.
ieee: K. Khamina et al., “Characterization of host proteins interacting with
the lymphocytic choriomeningitis virus L protein,” PLoS Pathogens, vol.
13, no. 12. Public Library of Science, 2017.
ista: Khamina K, Lercher A, Caldera M, Schliehe C, Vilagos B, Sahin M, Kosack L,
Bhattacharya A, Májek P, Stukalov A, Sacco R, James L, Pinschewer D, Bennett K,
Menche J, Bergthaler A. 2017. Characterization of host proteins interacting with
the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 13(12), e1006758.
mla: Khamina, Kseniya, et al. “Characterization of Host Proteins Interacting with
the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens, vol.
13, no. 12, e1006758, Public Library of Science, 2017, doi:10.1371/journal.ppat.1006758.
short: K. Khamina, A. Lercher, M. Caldera, C. Schliehe, B. Vilagos, M. Sahin, L.
Kosack, A. Bhattacharya, P. Májek, A. Stukalov, R. Sacco, L. James, D. Pinschewer,
K. Bennett, J. Menche, A. Bergthaler, PLoS Pathogens 13 (2017).
date_created: 2018-12-11T11:47:03Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2021-01-12T08:01:48Z
day: '01'
ddc:
- '576'
- '616'
department:
- _id: GaNo
doi: 10.1371/journal.ppat.1006758
file:
- access_level: open_access
checksum: 1aa20f19a1e90664fadce6e7d5284fdc
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:26Z
date_updated: 2020-07-14T12:46:44Z
file_id: '4944'
file_name: IST-2018-931-v1+1_journal.ppat.1006758.pdf
file_size: 4106772
relation: main_file
file_date_updated: 2020-07-14T12:46:44Z
has_accepted_license: '1'
intvolume: ' 13'
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: PLoS Pathogens
publication_identifier:
issn:
- '15537366'
publication_status: published
publisher: Public Library of Science
publist_id: '7276'
pubrep_id: '931'
quality_controlled: '1'
scopus_import: 1
status: public
title: Characterization of host proteins interacting with the lymphocytic choriomeningitis
virus L protein
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2017'
...
---
_id: '1228'
abstract:
- lang: eng
text: Since 2006, reprogrammed cells have increasingly been used as a biomedical
research technique in addition to neuro-psychiatric methods. These rapidly evolving
techniques allow for the generation of neuronal sub-populations, and have sparked
interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic
and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder
(BPD). This review provides a summary of 19 publications on reprogrammed adult
somatic cells derived from patients with SCZ, and five publications using this
technique in patients with BPD. As both disorders are complex and heterogeneous,
there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations
of dopaminergic transmission in vitro are sparse, despite the great explanatory
power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations
of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental
alterations. Some studies also report on the efficacy of medicinal compounds to
revert alterations observed in cellular models. However, due to the paucity of
replication studies, no comprehensive conclusions can be drawn from studies using
reprogrammed cells at the present time. In the future, findings from cell culture
methods need to be integrated with clinical, epidemiological, pharmacological
and imaging data in order to generate a more comprehensive picture of SCZ and
BPD.
acknowledgement: This work was supported by grants of the Austrian Science Fund (FWF)
P23585B09 to M.W. and F3506 to H.H.S. and the “Wiener Wissenschafts-, Forschungs-
und Technologiefonds” (Vienna Science and Technology Fund; WWTF) CS15-033 to M.W.
article_processing_charge: No
article_type: review
author:
- first_name: Ulrich
full_name: Sauerzopf, Ulrich
last_name: Sauerzopf
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Marco
full_name: Niello, Marco
last_name: Niello
- first_name: Ana
full_name: Weidenauer, Ana
last_name: Weidenauer
- first_name: Nicole
full_name: Praschak Rieder, Nicole
last_name: Praschak Rieder
- first_name: Harald
full_name: Sitte, Harald
last_name: Sitte
- first_name: Matthaeus
full_name: Willeit, Matthaeus
last_name: Willeit
citation:
ama: Sauerzopf U, Sacco R, Novarino G, et al. Are reprogrammed cells a useful tool
for studying dopamine dysfunction in psychotic disorders? A review of the current
evidence. European Journal of Neuroscience. 2017;45(1):45-57. doi:10.1111/ejn.13418
apa: Sauerzopf, U., Sacco, R., Novarino, G., Niello, M., Weidenauer, A., Praschak
Rieder, N., … Willeit, M. (2017). Are reprogrammed cells a useful tool for studying
dopamine dysfunction in psychotic disorders? A review of the current evidence.
European Journal of Neuroscience. Wiley-Blackwell. https://doi.org/10.1111/ejn.13418
chicago: Sauerzopf, Ulrich, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer,
Nicole Praschak Rieder, Harald Sitte, and Matthaeus Willeit. “Are Reprogrammed
Cells a Useful Tool for Studying Dopamine Dysfunction in Psychotic Disorders?
A Review of the Current Evidence.” European Journal of Neuroscience. Wiley-Blackwell,
2017. https://doi.org/10.1111/ejn.13418.
ieee: U. Sauerzopf et al., “Are reprogrammed cells a useful tool for studying
dopamine dysfunction in psychotic disorders? A review of the current evidence,”
European Journal of Neuroscience, vol. 45, no. 1. Wiley-Blackwell, pp.
45–57, 2017.
ista: Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak Rieder
N, Sitte H, Willeit M. 2017. Are reprogrammed cells a useful tool for studying
dopamine dysfunction in psychotic disorders? A review of the current evidence.
European Journal of Neuroscience. 45(1), 45–57.
mla: Sauerzopf, Ulrich, et al. “Are Reprogrammed Cells a Useful Tool for Studying
Dopamine Dysfunction in Psychotic Disorders? A Review of the Current Evidence.”
European Journal of Neuroscience, vol. 45, no. 1, Wiley-Blackwell, 2017,
pp. 45–57, doi:10.1111/ejn.13418.
short: U. Sauerzopf, R. Sacco, G. Novarino, M. Niello, A. Weidenauer, N. Praschak
Rieder, H. Sitte, M. Willeit, European Journal of Neuroscience 45 (2017) 45–57.
date_created: 2018-12-11T11:50:50Z
date_published: 2017-01-01T00:00:00Z
date_updated: 2023-09-20T11:16:01Z
day: '01'
ddc:
- '616'
department:
- _id: GaNo
doi: 10.1111/ejn.13418
external_id:
isi:
- '000392487100005'
pmid:
- '27690184'
file:
- access_level: open_access
checksum: c572cf02be8fbb7020cfcfb892182e4c
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:10:48Z
date_updated: 2020-07-14T12:44:39Z
file_id: '4838'
file_name: IST-2017-738-v1+1_Sauerzopf_et_al-2017-European_Journal_of_Neuroscience.pdf
file_size: 169145
relation: main_file
file_date_updated: 2020-07-14T12:44:39Z
has_accepted_license: '1'
intvolume: ' 45'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 45 - 57
pmid: 1
publication: European Journal of Neuroscience
publication_status: published
publisher: Wiley-Blackwell
publist_id: '6106'
pubrep_id: '738'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic
disorders? A review of the current evidence
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 45
year: '2017'
...
---
_id: '460'
abstract:
- lang: eng
text: NF-κB signaling is a central pathway of immunity and integrates signal transduction
upon a wide array of inflammatory stimuli. Noncanonical NF-κB signaling is activated
by a small subset of TNF family receptors and characterized by NF-κB2/p52 transcriptional
activity. The medical relevance of this pathway has recently re-emerged from the
discovery of primary immunodeficiency patients that have loss-of-function mutations
in the MAP3K14 gene encoding NIK. Nevertheless, knowledge of protein interactions
that regulate noncanonical NF-κB signaling is sparse. Here we report a detailed
state-of-the-art mass spectrometry-based protein–protein interaction network including
the noncanonical NF-κB signaling nodes TRAF2, TRAF3, IKKα, NIK, and NF-κB2/p100.
The value of the data set was confirmed by the identification of interactions
already known to regulate this pathway. In addition, a remarkable number of novel
interactors were identified. We provide validation of the novel NIK and IKKα interactor
FKBP8, which may regulate processes downstream of noncanonical NF-κB signaling.
To understand perturbed noncanonical NF-κB signaling in the context of misregulated
NIK in disease, we also provide a differential interactome of NIK mutants that
cause immunodeficiency. Altogether, this data set not only provides critical insight
into how protein–protein interactions can regulate immune signaling but also offers
a novel resource on noncanonical NF-κB signaling.
acknowledgement: "Austrian Science Fund (FWF) Lise Meitner Program Fellowship (FWF
M-1809, to K.L.W.), FWF Infect-ERA framework (I-1620_B22, to S.K.), European Research
Council (ERC StG 310857, to K.B.)\nWe thank Jacques Colinge, André C. Müller, and
Peter Májek for fruitful discussions and Elisabeth Salzer and Kate G. Ackermann
for critically reading the manuscript. We thank Giulio Superti-Furga for providing
pTO-SII-HA-GW plasmids. \n\n"
author:
- first_name: Katharina
full_name: Willmann, Katharina L
last_name: Willmann
- first_name: Roberto
full_name: Roberto Sacco
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Rui
full_name: Martins, Rui
last_name: Martins
- first_name: Wojciech
full_name: Garncarz, Wojciech
last_name: Garncarz
- first_name: Ana
full_name: Krolo, Ana
last_name: Krolo
- first_name: Sylvia
full_name: Knapp, Sylvia
last_name: Knapp
- first_name: Keiryn
full_name: Bennett, Keiryn L
last_name: Bennett
- first_name: Kaan
full_name: Boztug, Kaan
last_name: Boztug
citation:
ama: Willmann K, Sacco R, Martins R, et al. Expanding the interactome of the noncanonical
NF-κB signaling pathway. Journal of Proteome Research. 2016;15(9):2900-2909.
doi:10.1021/acs.jproteome.5b01004
apa: Willmann, K., Sacco, R., Martins, R., Garncarz, W., Krolo, A., Knapp, S., …
Boztug, K. (2016). Expanding the interactome of the noncanonical NF-κB signaling
pathway. Journal of Proteome Research. American Chemical Society. https://doi.org/10.1021/acs.jproteome.5b01004
chicago: Willmann, Katharina, Roberto Sacco, Rui Martins, Wojciech Garncarz, Ana
Krolo, Sylvia Knapp, Keiryn Bennett, and Kaan Boztug. “Expanding the Interactome
of the Noncanonical NF-ΚB Signaling Pathway.” Journal of Proteome Research.
American Chemical Society, 2016. https://doi.org/10.1021/acs.jproteome.5b01004.
ieee: K. Willmann et al., “Expanding the interactome of the noncanonical
NF-κB signaling pathway,” Journal of Proteome Research, vol. 15, no. 9.
American Chemical Society, pp. 2900–2909, 2016.
ista: Willmann K, Sacco R, Martins R, Garncarz W, Krolo A, Knapp S, Bennett K, Boztug
K. 2016. Expanding the interactome of the noncanonical NF-κB signaling pathway.
Journal of Proteome Research. 15(9), 2900–2909.
mla: Willmann, Katharina, et al. “Expanding the Interactome of the Noncanonical
NF-ΚB Signaling Pathway.” Journal of Proteome Research, vol. 15, no. 9,
American Chemical Society, 2016, pp. 2900–09, doi:10.1021/acs.jproteome.5b01004.
short: K. Willmann, R. Sacco, R. Martins, W. Garncarz, A. Krolo, S. Knapp, K. Bennett,
K. Boztug, Journal of Proteome Research 15 (2016) 2900–2909.
date_created: 2018-12-11T11:46:36Z
date_published: 2016-07-15T00:00:00Z
date_updated: 2021-01-12T08:00:24Z
day: '15'
doi: 10.1021/acs.jproteome.5b01004
extern: 1
intvolume: ' 15'
issue: '9'
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295629/
month: '07'
oa: 1
page: 2900 - 2909
publication: Journal of Proteome Research
publication_status: published
publisher: American Chemical Society
publist_id: '7361'
quality_controlled: 0
status: public
title: Expanding the interactome of the noncanonical NF-κB signaling pathway
type: journal_article
volume: 15
year: '2016'
...