---
_id: '12275'
abstract:
- lang: eng
text: N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting
the secretory pathway and have been implicated in protein folding, stability,
and localization. Mutations in genes important for N-glycosylation result in congenital
disorders of glycosylation that are often associated with intellectual disability.
Here, we show that structurally distinct N-glycans regulate an extracellular protein
complex involved in the patterning of somatosensory dendrites in Caenorhabditis
elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme
in the biosynthesis of specific N-glycans, regulates the activity of the Menorin
adhesion complex without obviously affecting the protein stability and localization
of its components. AMAN-2 functions cell-autonomously to allow for decoration
of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose
N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites
regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular
proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures
regulate dendrite patterning by coordinating the activity of an extracellular
adhesion complex, suggesting that the molecular diversity of N-glycans can contribute
to developmental specificity in the nervous system.
acknowledgement: 'We thank Scott Garforth, Sarah Garrett, Peri Kurshan, Yehuda Salzberg,
PamelaStanley, Robert Townley, and members of the B€ulow laboratory for commentson
the manuscript or helpful discussions during the course of this work. Wethank David
Miller, Shohei Mitani, Kang Shen, and Iain Wilson for reagents,and Yuji Kohara for
theyk11g705cDNA clone. We are grateful to MeeraTrivedi for sharing thedzIs117strain
prior to publication. Some strains wereprovided by the Caenorhabditis Genome Center
(funded by the NIH Office ofResearch Infrastructure Programs P40OD010440). This
work was supportedby grants from the National Institute of Health (NIH): R01NS096672andR21NS111145to
HEB; F31NS100370to MR; T32GM007288and F31HD066967to CADB; P30HD071593to Albert Einstein
College of Medicine. We acknowl-edge support to MR by the Department of Neuroscience.
NJRS was the recipi-ent of a Colciencias-Fulbright Fellowship and HEB of an Irma
T. Hirschl/Monique Weill-Caulier research fellowship'
article_number: e54163
article_processing_charge: No
article_type: original
author:
- first_name: Maisha
full_name: Rahman, Maisha
last_name: Rahman
- first_name: Nelson
full_name: Ramirez, Nelson
id: 39831956-E4FE-11E9-85DE-0DC7E5697425
last_name: Ramirez
- first_name: Carlos A
full_name: Diaz‐Balzac, Carlos A
last_name: Diaz‐Balzac
- first_name: Hannes E
full_name: Bülow, Hannes E
last_name: Bülow
citation:
ama: Rahman M, Ramirez N, Diaz‐Balzac CA, Bülow HE. Specific N-glycans regulate
an extracellular adhesion complex during somatosensory dendrite patterning. EMBO
Reports. 2022;23(7). doi:10.15252/embr.202154163
apa: Rahman, M., Ramirez, N., Diaz‐Balzac, C. A., & Bülow, H. E. (2022). Specific
N-glycans regulate an extracellular adhesion complex during somatosensory dendrite
patterning. EMBO Reports. Embo Press. https://doi.org/10.15252/embr.202154163
chicago: Rahman, Maisha, Nelson Ramirez, Carlos A Diaz‐Balzac, and Hannes E Bülow.
“Specific N-Glycans Regulate an Extracellular Adhesion Complex during Somatosensory
Dendrite Patterning.” EMBO Reports. Embo Press, 2022. https://doi.org/10.15252/embr.202154163.
ieee: M. Rahman, N. Ramirez, C. A. Diaz‐Balzac, and H. E. Bülow, “Specific N-glycans
regulate an extracellular adhesion complex during somatosensory dendrite patterning,”
EMBO Reports, vol. 23, no. 7. Embo Press, 2022.
ista: Rahman M, Ramirez N, Diaz‐Balzac CA, Bülow HE. 2022. Specific N-glycans regulate
an extracellular adhesion complex during somatosensory dendrite patterning. EMBO
Reports. 23(7), e54163.
mla: Rahman, Maisha, et al. “Specific N-Glycans Regulate an Extracellular Adhesion
Complex during Somatosensory Dendrite Patterning.” EMBO Reports, vol. 23,
no. 7, e54163, Embo Press, 2022, doi:10.15252/embr.202154163.
short: M. Rahman, N. Ramirez, C.A. Diaz‐Balzac, H.E. Bülow, EMBO Reports 23 (2022).
date_created: 2023-01-16T10:01:44Z
date_published: 2022-07-05T00:00:00Z
date_updated: 2023-10-03T11:25:54Z
day: '05'
department:
- _id: MaDe
doi: 10.15252/embr.202154163
external_id:
isi:
- '000797302700001'
pmid:
- '35586945'
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
issue: '7'
keyword:
- Genetics
- Molecular Biology
- Biochemistry
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.15252/embr.202154163
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: EMBO Reports
publication_identifier:
eissn:
- 1469-3178
issn:
- 1469-221X
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Specific N-glycans regulate an extracellular adhesion complex during somatosensory
dendrite patterning
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2022'
...
---
_id: '11637'
abstract:
- lang: eng
text: The ability to detect and respond to acute oxygen (O2) shortages is indispensable
to aerobic life. The molecular mechanisms and circuits underlying this capacity
are poorly understood. Here, we characterize the behavioral responses of feeding
Caenorhabditis elegans to approximately 1% O2. Acute hypoxia triggers a bout of
turning maneuvers followed by a persistent switch to rapid forward movement as
animals seek to avoid and escape hypoxia. While the behavioral responses to 1%
O2 closely resemble those evoked by 21% O2, they have distinct molecular and circuit
underpinnings. Disrupting phosphodiesterases (PDEs), specific G proteins, or BBSome
function inhibits escape from 1% O2 due to increased cGMP signaling. A primary
source of cGMP is GCY-28, the ortholog of the atrial natriuretic peptide (ANP)
receptor. cGMP activates the protein kinase G EGL-4 and enhances neuroendocrine
secretion to inhibit acute responses to 1% O2. Triggering a rise in cGMP optogenetically
in multiple neurons, including AIA interneurons, rapidly and reversibly inhibits
escape from 1% O2. Ca2+ imaging reveals that a 7% to 1% O2 stimulus evokes a Ca2+
decrease in several neurons. Defects in mitochondrial complex I (MCI) and mitochondrial
complex I (MCIII), which lead to persistently high reactive oxygen species (ROS),
abrogate acute hypoxia responses. In particular, repressing the expression of
isp-1, which encodes the iron sulfur protein of MCIII, inhibits escape from 1%
O2 without affecting responses to 21% O2. Both genetic and pharmacological up-regulation
of mitochondrial ROS increase cGMP levels, which contribute to the reduced hypoxia
responses. Our results implicate ROS and precise regulation of intracellular cGMP
in the modulation of acute responses to hypoxia by C. elegans.
acknowledgement: ' This work was funded by H2020 European Research Council (ERC Advanced
grant, 269058 ACMO, https://erc.europa.eu/funding/advanced-grants) and Wellcome
Trust UK (Wellcome Investigator Award, 209504/Z/17/Z, https://wellcome.org/grant-funding/people-and-projects/grants-awarded/molecular-mechanisms-neural-circuit-function-0)
to M.d.B, and by H2020 European Research Council (ERC starting grant, 802653 OXYGEN
SENSING, https://erc.europa.eu/funding/starting-grants) and Vetenskapsrådet (VR
starting grant, 2018-02216, https://www.vr.se/english.html) to C.C. The funders
had no role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.'
article_number: e3001684
article_processing_charge: No
article_type: original
author:
- first_name: Lina
full_name: Zhao, Lina
last_name: Zhao
- first_name: Lorenz A.
full_name: Fenk, Lorenz A.
last_name: Fenk
- first_name: Lars
full_name: Nilsson, Lars
last_name: Nilsson
- first_name: Niko Paresh
full_name: Amin-Wetzel, Niko Paresh
id: E95D3014-9D8C-11E9-9C80-D2F8E5697425
last_name: Amin-Wetzel
- first_name: Nelson
full_name: Ramirez, Nelson
id: 39831956-E4FE-11E9-85DE-0DC7E5697425
last_name: Ramirez
- first_name: Mario
full_name: De Bono, Mario
id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
last_name: De Bono
orcid: 0000-0001-8347-0443
- first_name: Changchun
full_name: Chen, Changchun
last_name: Chen
citation:
ama: Zhao L, Fenk LA, Nilsson L, et al. ROS and cGMP signaling modulate persistent
escape from hypoxia in Caenorhabditis elegans. PLoS Biology. 2022;20(6).
doi:10.1371/journal.pbio.3001684
apa: Zhao, L., Fenk, L. A., Nilsson, L., Amin-Wetzel, N. P., Ramirez, N., de Bono,
M., & Chen, C. (2022). ROS and cGMP signaling modulate persistent escape from
hypoxia in Caenorhabditis elegans. PLoS Biology. Public Library of Science.
https://doi.org/10.1371/journal.pbio.3001684
chicago: Zhao, Lina, Lorenz A. Fenk, Lars Nilsson, Niko Paresh Amin-Wetzel, Nelson
Ramirez, Mario de Bono, and Changchun Chen. “ROS and CGMP Signaling Modulate Persistent
Escape from Hypoxia in Caenorhabditis Elegans.” PLoS Biology. Public Library
of Science, 2022. https://doi.org/10.1371/journal.pbio.3001684.
ieee: L. Zhao et al., “ROS and cGMP signaling modulate persistent escape
from hypoxia in Caenorhabditis elegans,” PLoS Biology, vol. 20, no. 6.
Public Library of Science, 2022.
ista: Zhao L, Fenk LA, Nilsson L, Amin-Wetzel NP, Ramirez N, de Bono M, Chen C.
2022. ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis
elegans. PLoS Biology. 20(6), e3001684.
mla: Zhao, Lina, et al. “ROS and CGMP Signaling Modulate Persistent Escape from
Hypoxia in Caenorhabditis Elegans.” PLoS Biology, vol. 20, no. 6, e3001684,
Public Library of Science, 2022, doi:10.1371/journal.pbio.3001684.
short: L. Zhao, L.A. Fenk, L. Nilsson, N.P. Amin-Wetzel, N. Ramirez, M. de Bono,
C. Chen, PLoS Biology 20 (2022).
date_created: 2022-07-24T22:01:42Z
date_published: 2022-06-21T00:00:00Z
date_updated: 2023-08-03T12:11:44Z
day: '21'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.1371/journal.pbio.3001684
external_id:
isi:
- '000828679600001'
pmid:
- '35727855'
file:
- access_level: open_access
checksum: df4902f854ad76769d3203bfdc69f16c
content_type: application/pdf
creator: dernst
date_created: 2022-07-25T07:38:49Z
date_updated: 2022-07-25T07:38:49Z
file_id: '11643'
file_name: 2022_PLoSBiology_Zhao.pdf
file_size: 3721585
relation: main_file
success: 1
file_date_updated: 2022-07-25T07:38:49Z
has_accepted_license: '1'
intvolume: ' 20'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 23870BE8-32DE-11EA-91FC-C7463DDC885E
grant_number: 209504/A/17/Z
name: Molecular mechanisms of neural circuit function
publication: PLoS Biology
publication_identifier:
eissn:
- 1545-7885
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis
elegans
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: 20
year: '2022'
...