Evidence map›Paper›PMID 36197591›Full record

ArticleMolecular neurobiology2022

Deconstruction of Neurotrypsin Reveals a Multi-factorially Regulated Activity Affecting Myotube Formation and Neuronal Excitability.

Anselmo Canciani, Cristina Capitanio, Serena Stanga, Silvia Faravelli, Luigi Scietti, Lisa Mapelli, Teresa Soda, Egidio D'Angelo, Pascal Kienlen-Campard, Federico Forneris

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 42% of its field
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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Anselmo CancianiThe Armenise-Harvard Laboratory of Structural Biology, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9/A, 27100, Pavia, Italy. anselmo.canciani@iusspavia.it.
Cristina CapitanioThe Armenise-Harvard Laboratory of Structural Biology, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9/A, 27100, Pavia, Italy.
Serena StangaAging and Dementia Research Group, CEMO Department, Institute of Neuroscience, UCLouvain, B-1200, Brussels, Belgium.
Silvia FaravelliThe Armenise-Harvard Laboratory of Structural Biology, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9/A, 27100, Pavia, Italy.
Luigi SciettiThe Armenise-Harvard Laboratory of Structural Biology, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9/A, 27100, Pavia, Italy.
Lisa MapelliDepartment of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100, Pavia, Italy.
Teresa SodaDepartment of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100, Pavia, Italy.
Egidio D'AngeloDepartment of Brain and Behavioral Sciences, University of Pavia, Via Forlanini 6, 27100, Pavia, Italy.
Pascal Kienlen-CampardAging and Dementia Research Group, CEMO Department, Institute of Neuroscience, UCLouvain, B-1200, Brussels, Belgium.
Federico FornerisThe Armenise-Harvard Laboratory of Structural Biology, Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9/A, 27100, Pavia, Italy. federico.forneris@unipv.it.ORCID http://orcid.org/0000-0002-7818-1804
University of Pavia · ITNeuroscience Institute · IT

Funding

EMBO Short-term fellowship #7677Fondazione Cariplo 2014-0881Giovanni Armenise-Harvard Foundation CDA 2013Horizon 2020 Framework Programme Grant Agreement No. 945539Horizon 2020 Framework Programme Human Brain Project SGA3Ministero dell'Istruzione, dell'Università e della Ricerca Dipartimenti di Eccellenza 2018-2022Ministero dell'Istruzione, dell'Università e della Ricerca Rita Levi-Montalcini Award
6 · The paper itself

Abstract

Neurotrypsin (NT) is a highly specific nervous system multi-domain serine protease best known for its selective processing of the potent synaptic organizer agrin. Its enzymatic activity is thought to influence processes of synaptic plasticity, with its deregulation causing accelerated neuromuscular junction (NMJ) degeneration or contributing to forms of mental retardation. These biological effects are likely to stem from NT-based regulation of agrin signaling. However, dissecting the exact biological implications of NT-agrin interplay is difficult, due to the scarce molecular detail regarding NT activity and NT-agrin interactions. We developed a strategy to reliably produce and purify a catalytically competent engineered variant of NT called "NT-mini" and a library of C-terminal agrin fragments, with which we performed a thorough biochemical and biophysical characterization of NT enzyme functionality. We studied the regulatory effects of calcium ions and heparin, identified NT's heparin-binding domain, and discovered how zinc ions induce modulation of enzymatic activity. Additionally, we investigated myotube differentiation and hippocampal neuron excitability, evidencing a dose-dependent increase in neuronal activity alongside a negative impact on myoblast fusion when using the active NT enzyme. Collectively, our results provide in vitro and cellular foundations to unravel the molecular underpinnings and biological significance of NT-agrin interactions.

Indexed as

AgrinMuscle Fibers, SkeletalHeparinNeuronsSerine EndopeptidasesSynapsesAgrinHeparinneurotrypsinSerine EndopeptidasesAgrin signalingNeuromuscular junctionNeurotrypsinProteolytic regulationSerine proteaseSynapses

Identifiers

PMID36197591
PMCPMC9616769
OpenAlexW4302027374

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.