Evidence map›Paper›PMID 38496415›Full record

ArticlebioRxiv : the preprint server for biology2024

Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors.

Kiall F Suazo, Vartika Mishra, Sanjay Maity, Shelby A Auger, Katarzyna Justyna, Alex Petre, Linda Ottoboni, Jessica Ongaro, Stefania P Corti, Francesco Lotti and 2 more

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Kiall F SuazoDepartment of Chemistry, University of Minnesota, Minneapolis, MN USA 55455.ORCID 0000-0002-0803-8332
Vartika MishraCenter for Motor Neuron Biology and Diseases, Department of Neurology. Columbia University Irving Medical Center. New York, NY 10032.
Sanjay MaityDepartment of Chemistry, University of Minnesota, Minneapolis, MN USA 55455.ORCID 0000-0003-2299-8409
Shelby A AugerDepartment of Chemistry, University of Minnesota, Minneapolis, MN USA 55455.ORCID 0000-0003-2873-2580
Katarzyna JustynaDepartment of Chemistry, University of Minnesota, Minneapolis, MN USA 55455.ORCID 0000-0003-4630-1581
Alex PetreDepartment of Chemistry, University of Minnesota, Minneapolis, MN USA 55455.ORCID 0000-0003-2818-6073
Linda OttoboniDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.ORCID 0000-0001-5412-7785
Jessica OngaroNeurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0003-2715-5355
Stefania P CortiDepartment of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.ORCID 0000-0001-5425-969X
Francesco LottiCenter for Motor Neuron Biology and Diseases, Department of Neurology. Columbia University Irving Medical Center. New York, NY 10032.ORCID 0000-0002-5104-9088
Serge PrzedborskiCenter for Motor Neuron Biology and Diseases, Department of Neurology. Columbia University Irving Medical Center. New York, NY 10032.ORCID 0000-0002-7283-3883
Mark D DistefanoDepartment of Chemistry, University of Minnesota, Minneapolis, MN USA 55455.ORCID 0000-0002-2872-0259
University of Minnesota · USColumbia University Irving Medical Center · USUniversity of Milan · ITFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · IT

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Training Grant: Functional Proteomics of AgingT32AG029796 · NIA · UNIVERSITY OF MINNESOTA · PI EDGAR A ARRIAGA, Douglas G Mashek · 2008 to 2026
$6.6M
Protein prenylation inhibition for the treatment of tauopathiesR01NS107442 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2018 to 2022
$3.1M
Training the Next Generation of Chemical BiologistsT32GM132029 · NIGMS · UNIVERSITY OF MINNESOTA · PI Erin Elizabeth Carlson, William Charles Krause Pomerantz · 2019 to 2026
$2.7M
Chemical Approaches for Exploring Protein Prenylation in Living CellsR35GM141853 · NIGMS · UNIVERSITY OF MINNESOTA · PI MARK D DISTEFANO · 2021 to 2026
$2.4M
SMN post-translational modification in Spinal Muscular AtrophyR21NS101575 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LOTTI, FRANCESCO · 2017 to 2018
$440k
NCI NIH HHS P30 CA077598NIA NIH HHS T32 AG029796NIGMS NIH HHS R35 GM141853NIGMS NIH HHS T32 GM132029NINDS NIH HHS R01 NS107442NINDS NIH HHS R21 NS101575
6 · The paper itself

Abstract

Protein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the synthesis of the alkyne-containing isoprenoid analogue C15AlkOPP are reported to improve synthetic efficiency. Next, metabolic labeling with C15AlkOPP was optimized to obtain useful levels of metabolic incorporation of the probe in several types of primary cells. Those conditions were then used to study the prenylomes of motor neurons (ES-MNs), astrocytes (ES-As), and their embryonic stem cell progenitors (ESCs), which allowed for the identification of 54 prenylated proteins from ESCs, 50 from ES-MNs and 84 from ES-As, representing all types of prenylation. Bioinformatic analysis revealed specific enriched pathways, including nervous system development, chemokine signaling, Rho GTPase signaling, and adhesion. Hierarchical clustering showed that most enriched pathways in all three cell types are related to GTPase activity and vesicular transport. In contrast, STRING analysis showed significant interactions in two populations that appear to be cell type dependent. The data provided herein demonstrates that robust incorporation of C15AlkOPP can be obtained in ES-MNs and related primary cells purified via magnetic-activated cell sorting allowing the identification and quantification of numerous prenylated proteins. These results suggest that metabolic labeling with C15AlkOPP should be an effective approach for investigating the role of prenylated proteins in primary cells in both normal cells and disease pathologies, including ALS.

Identifiers

PMID38496415
PMCPMC10942399
OpenAlexW4392503644

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.