Evidence map›Paper›PMID 31945187›Full record

ArticleJournal of neurochemistry2020

The endoplasmic reticulum acetyltransferases ATase1/NAT8B and ATase2/NAT8 are differentially regulated to adjust engagement of the secretory pathway.

Michael J Rigby, Yun Ding, Mark A Farrugia, Michael Feig, Giuseppe P Cortese, Heather Mitchell, Corinna Burger, Luigi Puglielli

Open access · greenAbstract read
In one paragraph

Article in Journal of neurochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Michael J RigbyDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0001-8809-2648
Yun DingDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Mark A FarrugiaDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Michael FeigDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Giuseppe P CorteseDepartment of Neurology, University of Wisconsin-Madison, Madison, WI, USA.
Heather MitchellRodent Models Core, Waisman Center, Madison, WI, USA.
Corinna BurgerNeuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA.
Luigi PuglielliDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0003-0259-8424
University of Wisconsin–Madison · USMichigan State University · USShanghai Model Organisms (China) · CN

Funding

Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Dorothy Farrar Edwards · 2019 to 2026
$34.5M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
Biology of Aging and Age-Related Diseases Training GrantT32AG000213 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Rozalyn M. Anderson, Sanjay Asthana · 1991 to 2026
$9.9M
Integrated Training For Physician-ScientistsT32GM140935 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Anna Huttenlocher, Jeniel E Nett · 2021 to 2026
$6.5M
Waisman Intellectual and Developmental Disabilities Research Center Down Syndrome RegistryU54HD090256 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI POLLAK, SETH D · 2016 to 2020
$6.0M
Spastic paraplegia, neurodegeneration and autism: possible role for AT- 1/SLC33A1?R01NS094154 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI Luigi Puglielli · 2015 to 2026
$4.3M
Acetyl-CoA flux and mitochondrial adaptation: a pathogenic role in aging and AD?RF1AG057408 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ANDERSON, ROZALYN M., PUGLIELLI, LUIGI · 2017 to 2017
$3.5M
Modeling and dynamics of biomolecules on cellular scalesR35GM126948 · NIGMS · MICHIGAN STATE UNIVERSITY · PI Michael Feig · 2018 to 2026
$3.2M
Proteostasis in the aging and Alzheimer's disease brain: are the ATases novel targets?RF1AG053937 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI PUGLIELLI, LUIGI · 2016 to 2016
$1.9M
Mechanisms of age related cognitive impairmentR01AG048172 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BURGER, CORINNA · 2014 to 2018
$1.5M
Novel mechanisms for Alzheimer disease prevention and or treatmentI01BX004202 · VA · WM S. MIDDLETON MEMORIAL VETERANS HOSP · PI PUGLIELLI, LUIGI · 2019 to 2022
–
BLRD VA I01 BX004202NIA NIH HHS P30 AG062715NIA NIH HHS R01 AG048172NIA NIH HHS RF1 AG053937NIA NIH HHS RF1 AG057408NIA NIH HHS T32 AG000213NICHD NIH HHS U54 HD090256NIGMS NIH HHS R35 GM126948NIGMS NIH HHS T32 GM008692NIGMS NIH HHS T32 GM140935NINDS NIH HHS R01 NS094154
6 · The paper itself

Abstract

Nε-lysine acetylation of nascent glycoproteins within the endoplasmic reticulum (ER) lumen regulates the efficiency of the secretory pathway. The ER acetylation machinery consists of the membrane transporter, acetyl-CoA transporter 1 (AT-1/SLC33A1), and two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Dysfunctional ER acetylation is associated with severe neurological diseases with duplication of AT-1/SLC33A1 being associated with autism spectrum disorder, intellectual disability, and dysmorphism. Neuron-specific AT-1 over-expression in the mouse alters neuron morphology and function, causing an autism-like phenotype, indicating that ER acetylation plays a key role in neurophysiology. As such, characterizing the molecular mechanisms that regulate the acetylation machinery could reveal critical information about its biology. By using structure-biochemistry approaches, we discovered that ATase1 and ATase2 share enzymatic properties but differ in that ATase1 is post-translationally regulated via acetylation. Furthermore, gene expression studies revealed that the promoters of AT-1, ATase1, and ATase2 contain functional binding sites for the neuron-related transcription factors cAMP response element-binding protein and the immediate-early genes c-FOS and c-JUN, and that ATase1 and ATase2 exhibit additional modes of transcriptional regulation relevant to aging and Alzheimer's disease. In vivo rodent gene expression experiments revealed that Atase2 is specifically induced following activity-dependent events. Finally, over-expression of either ATase1 or ATase2 was sufficient to increase the engagement of the secretory pathway in PC12 cells. Our results indicate important regulatory roles for ATase1 and ATase2 in neuron function with induction of ATase2 expression potentially serving as a critical event that adjusts the efficiency of the secretory pathway for activity-dependent neuronal functions.

Indexed as

AcetylationAcetyltransferasesAnimalsEndoplasmic ReticulumHumansMaleMiceMice, Inbred C57BLNeuronal PlasticityNeuronsPC12 CellsProtein Processing, Post-TranslationalRatsRats, Inbred F344Secretory PathwayTranscription, GeneticAcetyltransferasesacetyltransferaseATase1ATase2endoplasmic reticulumNε-lysine acetylationsecretory pathway

Identifiers

PMID31945187
PMCPMC7363514
OpenAlexW2999738434

What OpenQuestion holds

Textmetadata
LicenceTDM
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.