---
_id: '12224'
abstract:
- lang: eng
text: Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane
receptor trafficking. However, its influence on intrinsic brain activity and corresponding
behavioral processes remains unclear. Here we show that murine Mkln1
knockout causes non-habituating locomotor activity, increased exploratory drive,
and decreased locomotor response to amphetamine. Muskelin deficiency impairs social
novelty detection while promoting the retention of spatial reference memory and
fear extinction recall. This is strongly mirrored in either weaker or stronger
resting-state functional connectivity between critical circuits mediating locomotor
exploration and cognition. We show that Mkln1 deletion
alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated
synaptic transmission but selective impairment in synaptic potentiation maintenance.
We identify muskelin at excitatory synapses and highlight its role in regulating
dendritic spine actin stability. Our findings point to aberrant spine actin modulation
and changes in glutamatergic synaptic function as critical mechanisms that contribute
to the neurobehavioral phenotype arising from Mkln1
ablation.
acknowledgement: "The authors are grateful to the UKE Animal Facilities (Hamburg)
for animal husbandry and Dr. Bastian Tiemann for his veterinary expertise and supervision
of animal care. We thank Dr. Franco Lombino for critically reading the manuscript
and for helpful discussion. This work was supported by grants from the Deutsche
Forschungsgemeinschaft (DFG) (FOR2419-KN556/11-1, FOR2419-KN556/11-2, KN556/12-1)
and the Landesforschungsförderung Hamburg (LFF-FV76) to M.K.\r\nOpen Access funding
enabled and organized by Projekt DEAL."
article_number: '589'
article_processing_charge: No
article_type: original
author:
- first_name: Mary W
full_name: Muhia, Mary W
id: ab7ed20f-09f7-11eb-909c-d5d0b443ee9d
last_name: Muhia
- first_name: PingAn
full_name: YuanXiang, PingAn
last_name: YuanXiang
- first_name: Jan
full_name: Sedlacik, Jan
last_name: Sedlacik
- first_name: Jürgen R.
full_name: Schwarz, Jürgen R.
last_name: Schwarz
- first_name: Frank F.
full_name: Heisler, Frank F.
last_name: Heisler
- first_name: Kira V.
full_name: Gromova, Kira V.
last_name: Gromova
- first_name: Edda
full_name: Thies, Edda
last_name: Thies
- first_name: Petra
full_name: Breiden, Petra
last_name: Breiden
- first_name: Yvonne
full_name: Pechmann, Yvonne
last_name: Pechmann
- first_name: Michael R.
full_name: Kreutz, Michael R.
last_name: Kreutz
- first_name: Matthias
full_name: Kneussel, Matthias
last_name: Kneussel
citation:
ama: Muhia MW, YuanXiang P, Sedlacik J, et al. Muskelin regulates actin-dependent
synaptic changes and intrinsic brain activity relevant to behavioral and cognitive
processes. Communications Biology. 2022;5. doi:10.1038/s42003-022-03446-1
apa: Muhia, M. W., YuanXiang, P., Sedlacik, J., Schwarz, J. R., Heisler, F. F.,
Gromova, K. V., … Kneussel, M. (2022). Muskelin regulates actin-dependent synaptic
changes and intrinsic brain activity relevant to behavioral and cognitive processes.
Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-022-03446-1
chicago: Muhia, Mary W, PingAn YuanXiang, Jan Sedlacik, Jürgen R. Schwarz, Frank
F. Heisler, Kira V. Gromova, Edda Thies, et al. “Muskelin Regulates Actin-Dependent
Synaptic Changes and Intrinsic Brain Activity Relevant to Behavioral and Cognitive
Processes.” Communications Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03446-1.
ieee: M. W. Muhia et al., “Muskelin regulates actin-dependent synaptic changes
and intrinsic brain activity relevant to behavioral and cognitive processes,”
Communications Biology, vol. 5. Springer Nature, 2022.
ista: Muhia MW, YuanXiang P, Sedlacik J, Schwarz JR, Heisler FF, Gromova KV, Thies
E, Breiden P, Pechmann Y, Kreutz MR, Kneussel M. 2022. Muskelin regulates actin-dependent
synaptic changes and intrinsic brain activity relevant to behavioral and cognitive
processes. Communications Biology. 5, 589.
mla: Muhia, Mary W., et al. “Muskelin Regulates Actin-Dependent Synaptic Changes
and Intrinsic Brain Activity Relevant to Behavioral and Cognitive Processes.”
Communications Biology, vol. 5, 589, Springer Nature, 2022, doi:10.1038/s42003-022-03446-1.
short: M.W. Muhia, P. YuanXiang, J. Sedlacik, J.R. Schwarz, F.F. Heisler, K.V. Gromova,
E. Thies, P. Breiden, Y. Pechmann, M.R. Kreutz, M. Kneussel, Communications Biology
5 (2022).
date_created: 2023-01-16T09:48:19Z
date_published: 2022-06-15T00:00:00Z
date_updated: 2023-08-04T09:25:59Z
day: '15'
ddc:
- '570'
department:
- _id: PreCl
doi: 10.1038/s42003-022-03446-1
external_id:
isi:
- '000811777900003'
file:
- access_level: open_access
checksum: bd95be1e77090208b79bc45ea8785d0b
content_type: application/pdf
creator: dernst
date_created: 2023-01-27T08:23:46Z
date_updated: 2023-01-27T08:23:46Z
file_id: '12417'
file_name: 2022_CommBiology_Muhia.pdf
file_size: 3968356
relation: main_file
success: 1
file_date_updated: 2023-01-27T08:23:46Z
has_accepted_license: '1'
intvolume: ' 5'
isi: 1
keyword:
- General Agricultural and Biological Sciences
- General Biochemistry
- Genetics and Molecular Biology
- Medicine (miscellaneous)
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
publication: Communications Biology
publication_identifier:
issn:
- 2399-3642
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity
relevant to behavioral and cognitive processes
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 5
year: '2022'
...
---
_id: '10310'
abstract:
- lang: eng
text: A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI)
from Thermosynechococcus elongatus was reported as the first atomic model of PSI
almost 20 years ago. However, the monomeric PSI structure has not yet been reported
despite long-standing interest in its structure and extensive spectroscopic characterization
of the loss of red chlorophylls upon monomerization. Here, we describe the structure
of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the
trimer structure gave detailed insights into monomerization-induced changes in
both the central trimerization domain and the peripheral regions of the complex.
Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls
adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization
of red chlorophylls and that lipids of the surrounding membrane present a major
source of thermal energy for uphill excitation energy transfer from red chlorophylls
to P700.
acknowledgement: We are grateful for additional support and valuable scientific input
for this project by Yuko Misumi, Jiannan Li, Hisako Kubota-Kawai, Takeshi Kawabata,
Mian Wu, Eiki Yamashita, Atsushi Nakagawa, Volker Hartmann, Melanie Völkel and Matthias
Rögner. Parts of this research were funded by the German Research Council (DFG)
within the framework of GRK 2341 (Microbial Substrate Conversion) to M.M.N., the
Platform Project for Supporting Drug Discovery and Life Science Research [Basis
for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from
AMED under grant number JP20am0101117 (K.N.), JP16K07266 to Atsunori Oshima and
C.G., a Grants-in-Aid for Scientific Research under grant number JP 25000013 (K.N.),
17H03647 (C.G.) and 16H06560 (G.K.) from MEXT-KAKENHI, the International Joint Research
Promotion Program from Osaka University to M.M.N., C.G. and G.K., and the Cyclic
Innovation for Clinical Empowerment (CiCLE) Grant Number JP17pc0101020 from AMED
to K.N. and G.K.
article_number: '304'
article_processing_charge: No
article_type: original
author:
- first_name: Mehmet Orkun
full_name: Çoruh, Mehmet Orkun
id: d25163e5-8d53-11eb-a251-e6dd8ea1b8ef
last_name: Çoruh
orcid: 0000-0002-3219-2022
- first_name: Anna
full_name: Frank, Anna
last_name: Frank
- first_name: Hideaki
full_name: Tanaka, Hideaki
last_name: Tanaka
- first_name: Akihiro
full_name: Kawamoto, Akihiro
last_name: Kawamoto
- first_name: Eithar
full_name: El-Mohsnawy, Eithar
last_name: El-Mohsnawy
- first_name: Takayuki
full_name: Kato, Takayuki
last_name: Kato
- first_name: Keiichi
full_name: Namba, Keiichi
last_name: Namba
- first_name: Christoph
full_name: Gerle, Christoph
last_name: Gerle
- first_name: Marc M.
full_name: Nowaczyk, Marc M.
last_name: Nowaczyk
- first_name: Genji
full_name: Kurisu, Genji
last_name: Kurisu
citation:
ama: Çoruh MO, Frank A, Tanaka H, et al. Cryo-EM structure of a functional monomeric
Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster.
Communications Biology. 2021;4(1). doi:10.1038/s42003-021-01808-9
apa: Çoruh, M. O., Frank, A., Tanaka, H., Kawamoto, A., El-Mohsnawy, E., Kato, T.,
… Kurisu, G. (2021). Cryo-EM structure of a functional monomeric Photosystem I
from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications
Biology. Springer . https://doi.org/10.1038/s42003-021-01808-9
chicago: Çoruh, Mehmet Orkun, Anna Frank, Hideaki Tanaka, Akihiro Kawamoto, Eithar
El-Mohsnawy, Takayuki Kato, Keiichi Namba, Christoph Gerle, Marc M. Nowaczyk,
and Genji Kurisu. “Cryo-EM Structure of a Functional Monomeric Photosystem I from
Thermosynechococcus Elongatus Reveals Red Chlorophyll Cluster.” Communications
Biology. Springer , 2021. https://doi.org/10.1038/s42003-021-01808-9.
ieee: M. O. Çoruh et al., “Cryo-EM structure of a functional monomeric Photosystem
I from Thermosynechococcus elongatus reveals red chlorophyll cluster,” Communications
Biology, vol. 4, no. 1. Springer , 2021.
ista: Çoruh MO, Frank A, Tanaka H, Kawamoto A, El-Mohsnawy E, Kato T, Namba K, Gerle
C, Nowaczyk MM, Kurisu G. 2021. Cryo-EM structure of a functional monomeric Photosystem
I from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications
Biology. 4(1), 304.
mla: Çoruh, Mehmet Orkun, et al. “Cryo-EM Structure of a Functional Monomeric Photosystem
I from Thermosynechococcus Elongatus Reveals Red Chlorophyll Cluster.” Communications
Biology, vol. 4, no. 1, 304, Springer , 2021, doi:10.1038/s42003-021-01808-9.
short: M.O. Çoruh, A. Frank, H. Tanaka, A. Kawamoto, E. El-Mohsnawy, T. Kato, K.
Namba, C. Gerle, M.M. Nowaczyk, G. Kurisu, Communications Biology 4 (2021).
date_created: 2021-11-19T11:37:29Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2023-08-14T11:51:19Z
day: '08'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1038/s42003-021-01808-9
external_id:
isi:
- '000627440700001'
pmid:
- '33686186'
file:
- access_level: open_access
checksum: 8ffd39f2bba7152a2441802ff313bf0b
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-19T15:09:18Z
date_updated: 2021-11-19T15:09:18Z
file_id: '10318'
file_name: 2021_CommBio_Çoruh.pdf
file_size: 6030261
relation: main_file
success: 1
file_date_updated: 2021-11-19T15:09:18Z
has_accepted_license: '1'
intvolume: ' 4'
isi: 1
issue: '1'
keyword:
- general agricultural and biological Sciences
- general biochemistry
- genetics and molecular biology
- medicine (miscellaneous)
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Communications Biology
publication_identifier:
issn:
- 2399-3642
publication_status: published
publisher: 'Springer '
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus
elongatus reveals red chlorophyll cluster
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 4
year: '2021'
...
---
_id: '8592'
abstract:
- lang: eng
text: Glioblastoma is the most malignant cancer in the brain and currently incurable.
It is urgent to identify effective targets for this lethal disease. Inhibition
of such targets should suppress the growth of cancer cells and, ideally also precancerous
cells for early prevention, but minimally affect their normal counterparts. Using
genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor
cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility
of cells within the development hierarchy of glioma to the knockout of insulin‐like
growth factor I receptor (IGF1R) is determined not only by their oncogenic states,
but also by their cell identities/states. Knockout of IGF1R selectively disrupts
the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable
outcome of IGF1R knockout on cell growth requires the mutant cells to commit to
the OPC identity regardless of its development hierarchical status. At the molecular
level, oncogenic mutations reprogram the cellular network of OPCs and force them
to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally
available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed.
The findings reveal the cellular window of IGF1R targeting and establish IGF1R
as an effective target for the prevention and treatment of glioblastoma.
acknowledgement: The authors thank Drs. J. Eisen, QR. Lu, S. Duan, Z‐H. Li, W. Mo,
and Q. Wu for their critical comments on the manuscript. They also thank Dr. H.
Zong for providing the CKO_NG2‐CreER model. This work is supported by the National
Key Research and Development Program of China, Stem Cell and Translational Research
(2016YFA0101201 to C.L., 2016YFA0100303 to Y.J.W.), the National Natural Science
Foundation of China (81673035 and 81972915 to C.L., 81472722 to Y.J.W.), the Science
Foundation for Distinguished Young Scientists of Zhejiang Province (LR17H160001
to C.L.), Fundamental Research Funds for the Central Universities (2016QNA7023 and
2017QNA7028 to C.L.) and the Thousand Talent Program for Young Outstanding Scientists,
China (to C.L.), IST Austria institutional funds (to S.H.), European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation programme
(725780 LinPro to S.H.). C.L. is a scholar of K. C. Wong Education Foundation.
article_number: '2001724'
article_processing_charge: No
article_type: original
author:
- first_name: Anhao
full_name: Tian, Anhao
last_name: Tian
- first_name: Bo
full_name: Kang, Bo
last_name: Kang
- first_name: Baizhou
full_name: Li, Baizhou
last_name: Li
- first_name: Biying
full_name: Qiu, Biying
last_name: Qiu
- first_name: Wenhong
full_name: Jiang, Wenhong
last_name: Jiang
- first_name: Fangjie
full_name: Shao, Fangjie
last_name: Shao
- first_name: Qingqing
full_name: Gao, Qingqing
last_name: Gao
- first_name: Rui
full_name: Liu, Rui
last_name: Liu
- first_name: Chengwei
full_name: Cai, Chengwei
last_name: Cai
- first_name: Rui
full_name: Jing, Rui
last_name: Jing
- first_name: Wei
full_name: Wang, Wei
last_name: Wang
- first_name: Pengxiang
full_name: Chen, Pengxiang
last_name: Chen
- first_name: Qinghui
full_name: Liang, Qinghui
last_name: Liang
- first_name: Lili
full_name: Bao, Lili
last_name: Bao
- first_name: Jianghong
full_name: Man, Jianghong
last_name: Man
- first_name: Yan
full_name: Wang, Yan
last_name: Wang
- first_name: Yu
full_name: Shi, Yu
last_name: Shi
- first_name: Jin
full_name: Li, Jin
last_name: Li
- first_name: Minmin
full_name: Yang, Minmin
last_name: Yang
- first_name: Lisha
full_name: Wang, Lisha
last_name: Wang
- first_name: Jianmin
full_name: Zhang, Jianmin
last_name: Zhang
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Junming
full_name: Zhu, Junming
last_name: Zhu
- first_name: Xiuwu
full_name: Bian, Xiuwu
last_name: Bian
- first_name: Ying‐Jie
full_name: Wang, Ying‐Jie
last_name: Wang
- first_name: Chong
full_name: Liu, Chong
last_name: Liu
citation:
ama: Tian A, Kang B, Li B, et al. Oncogenic state and cell identity combinatorially
dictate the susceptibility of cells within glioma development hierarchy to IGF1R
targeting. Advanced Science. 2020;7(21). doi:10.1002/advs.202001724
apa: Tian, A., Kang, B., Li, B., Qiu, B., Jiang, W., Shao, F., … Liu, C. (2020).
Oncogenic state and cell identity combinatorially dictate the susceptibility of
cells within glioma development hierarchy to IGF1R targeting. Advanced Science.
Wiley. https://doi.org/10.1002/advs.202001724
chicago: Tian, Anhao, Bo Kang, Baizhou Li, Biying Qiu, Wenhong Jiang, Fangjie Shao,
Qingqing Gao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate
the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.”
Advanced Science. Wiley, 2020. https://doi.org/10.1002/advs.202001724.
ieee: A. Tian et al., “Oncogenic state and cell identity combinatorially
dictate the susceptibility of cells within glioma development hierarchy to IGF1R
targeting,” Advanced Science, vol. 7, no. 21. Wiley, 2020.
ista: Tian A, Kang B, Li B, Qiu B, Jiang W, Shao F, Gao Q, Liu R, Cai C, Jing R,
Wang W, Chen P, Liang Q, Bao L, Man J, Wang Y, Shi Y, Li J, Yang M, Wang L, Zhang
J, Hippenmeyer S, Zhu J, Bian X, Wang Y, Liu C. 2020. Oncogenic state and cell
identity combinatorially dictate the susceptibility of cells within glioma development
hierarchy to IGF1R targeting. Advanced Science. 7(21), 2001724.
mla: Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate
the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.”
Advanced Science, vol. 7, no. 21, 2001724, Wiley, 2020, doi:10.1002/advs.202001724.
short: A. Tian, B. Kang, B. Li, B. Qiu, W. Jiang, F. Shao, Q. Gao, R. Liu, C. Cai,
R. Jing, W. Wang, P. Chen, Q. Liang, L. Bao, J. Man, Y. Wang, Y. Shi, J. Li, M.
Yang, L. Wang, J. Zhang, S. Hippenmeyer, J. Zhu, X. Bian, Y. Wang, C. Liu, Advanced
Science 7 (2020).
date_created: 2020-10-01T09:44:13Z
date_published: 2020-11-04T00:00:00Z
date_updated: 2023-08-22T09:53:01Z
day: '04'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1002/advs.202001724
ec_funded: 1
external_id:
isi:
- '000573860700001'
file:
- access_level: open_access
checksum: 92818c23ecc70e35acfa671f3cfb9909
content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:07:24Z
date_updated: 2020-12-10T14:07:24Z
file_id: '8938'
file_name: 2020_AdvScience_Tian.pdf
file_size: 7835833
relation: main_file
success: 1
file_date_updated: 2020-12-10T14:07:24Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
issue: '21'
keyword:
- General Engineering
- General Physics and Astronomy
- General Materials Science
- Medicine (miscellaneous)
- General Chemical Engineering
- Biochemistry
- Genetics and Molecular Biology (miscellaneous)
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Advanced Science
publication_identifier:
issn:
- 2198-3844
publication_status: published
publisher: Wiley
quality_controlled: '1'
status: public
title: Oncogenic state and cell identity combinatorially dictate the susceptibility
of cells within glioma development hierarchy to IGF1R targeting
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 7
year: '2020'
...