ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
A structural and functional analysis of Nna1 in Purkinje cell degeneration (pcd) mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- AAV-based gene therapy ameliorates neurological deficits in a mouse model of childhood-onset neurodegeneration with cerebellar atrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The distinct initiation sites and processing activities of TTLL4 and TTLL7 in glutamylation of brain tubulin.The Journal of biological chemistry · 2023Article
- CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis.BMC biology · 2023Article
- Article
- TTLL1 and TTLL4 polyglutamylases are required for the neurodegenerative phenotypes in pcd mice.PLoS genetics · 2022Article
- The Childhood-Onset Neurodegeneration with Cerebellar Atrophy (CONDCA) Disease Caused byBiomedicines · 2021Review
- Nna1 gene deficiency triggers Purkinje neuron death by tubulin hyperglutamylation and ER dysfunction.JCI insight · 2020Article
- Use of gene expression profile to identify potentially relevant transcripts to myofibrillar fragmentation index trait.Functional & integrative genomics · 2020Article
- Role of Cytosolic Carboxypeptidase 5 in Neuronal Survival and Spermatogenesis.Scientific reports · 2017Article
- α-amanitin resistance in Drosophila melanogaster: A genome-wide association approach.PloS one · 2017Article
- Comparison of the enzymatic and functional properties of three cytosolic carboxypeptidase family members.The Journal of biological chemistry · 2015Article
- Bioinformatics Data Mining Approach Suggests Coexpression of AGTPBP1 with an ALS-linked Gene C9orf72.Journal of central nervous system disease · 2015Article
- Lack of Cytosolic Carboxypeptidase 1 Leads to Subfertility due to the Reduced Number of Antral Follicles in pcd3J-/- Females.PloS one · 2015Article
- C-terminomics screen for natural substrates of cytosolic carboxypeptidase 1 reveals processing of acidic protein C termini.Molecular & cellular proteomics : MCP · 2015Article
- The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational removal of acidic amino acids.Molecular biology of the cell · 2014Article
- From mice to men: lessons from mutant ataxic mice.Cerebellum & ataxias · 2014Review
- Cytosolic carboxypeptidase 5 removes α- and γ-linked glutamates from tubulin.The Journal of biological chemistry · 2013Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The axotomy-inducible enzyme Nna1 defines a subfamily of M14 metallocarboxypeptidases, and its mutation underlies the Purkinje cell degeneration (pcd) mouse. However, the relationship among its catalytic activity, substrate specificities, and the critical processes of neurodegeneration/axon regeneration is incompletely understood. Here we used a transgenic rescue strategy targeting expression of modified forms of Nna1 to Purkinje cells in pcd mice to determine structure-activity relationships for neuronal survival and in parallel characterized the enzymatic properties of purified recombinant Nna1. The Nna1 subfamily uniquely shares conserved substrate-determining residues with aspartoacylase that, when mutated, cause Canavan disease. Homologous mutations (D1007E and R1078E) inactivate Nna1 in vivo, as does mutation of its catalytic glutamate (E1094A), which implies that metabolism of acidic substrates is essential for neuronal survival. Consistent with reports that Nna1 is a tubulin glutamylase, recombinant Nna1-but not the catalytic mutants-removes glutamate from tubulin. Recombinant Nna1 metabolizes synthetic substrates with 2 or more C-terminal glutamate (but not aspartate) residues (V(max) for 3 glutamates is ∼7-fold higher than 2 glutamates although K(M) is similar). Catalysis is not ATP/GTP dependent, and mutating the ATP/GTP binding site of Nna1 has no effect in vivo. Nna1 is a monomeric enzyme essential for neuronal survival through hydrolysis of polyglutamate-containing substrates.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.