» Articles » PMID: 23154466

Nicotinamide Mononucleotide Adenylyltransferase Maintains Active Zone Structure by Stabilizing Bruchpilot

Overview
Journal EMBO Rep
Specialty Molecular Biology
Date 2012 Nov 17
PMID 23154466
Citations 16
Authors
Affiliations
Soon will be listed here.
Abstract

Active zones are specialized presynaptic structures critical for neurotransmission. We show that a neuronal maintenance factor, nicotinamide mononucleotide adenylyltransferase (NMNAT), is required for maintaining active zone structural integrity in Drosophila by interacting with the active zone protein, Bruchpilot (BRP), and shielding it from activity-induced ubiquitin-proteasome-mediated degradation. NMNAT localizes to the peri-active zone and interacts biochemically with BRP in an activity-dependent manner. Loss of NMNAT results in ubiquitination, mislocalization and aggregation of BRP, and subsequent active zone degeneration. We propose that, as a neuronal maintenance factor, NMNAT specifically maintains active zone structure by direct protein-protein interaction.

Citing Articles

Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration.

Danos J, Addemir M, McGettigan L, Summers D bioRxiv. 2025; .

PMID: 39803444 PMC: 11722262. DOI: 10.1101/2024.12.31.630780.


Bendless is essential for PINK1-Park mediated Mitofusin degradation under mitochondrial stress caused by loss of LRPPRC.

Cheramangalam R, Anand T, Pandey P, Balasubramanian D, Varghese R, Singhal N PLoS Genet. 2023; 19(4):e1010493.

PMID: 37098042 PMC: 10162545. DOI: 10.1371/journal.pgen.1010493.


Insights into nervous system repair from the fruit fly.

Coupe D, Bossing T Neuronal Signal. 2022; 6(1):NS20210051.

PMID: 35474685 PMC: 9008705. DOI: 10.1042/NS20210051.


Alpha-synucleinopathy reduces NMNAT3 protein levels and neurite formation that can be rescued by targeting the NAD+ pathway.

Parsons R, Kocinaj A, Ruiz Pulido G, Prendergast S, Parsons A, Facey P Hum Mol Genet. 2022; 31(17):2918-2933.

PMID: 35397003 PMC: 9433734. DOI: 10.1093/hmg/ddac077.


The Ubiquitinated Axon: Local Control of Axon Development and Function by Ubiquitin.

Pinto M, Tome D, Almeida R J Neurosci. 2021; 41(13):2796-2813.

PMID: 33789876 PMC: 8018891. DOI: 10.1523/JNEUROSCI.2251-20.2021.


References
1.
Garcia-Junco-Clemente P, Cantero G, Gomez-Sanchez L, Linares-Clemente P, Martinez-Lopez J, Lujan R . Cysteine string protein-alpha prevents activity-dependent degeneration in GABAergic synapses. J Neurosci. 2010; 30(21):7377-91. PMC: 6632397. DOI: 10.1523/JNEUROSCI.0924-10.2010. View

2.
Greaves J, Salaun C, Fukata Y, Fukata M, Chamberlain L . Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein. J Biol Chem. 2008; 283(36):25014-26. PMC: 2882233. DOI: 10.1074/jbc.M802140200. View

3.
Zhai R, Bellen H . The architecture of the active zone in the presynaptic nerve terminal. Physiology (Bethesda). 2004; 19:262-70. DOI: 10.1152/physiol.00014.2004. View

4.
Matz J, Gilyan A, Kolar A, McCarvill T, Krueger S . Rapid structural alterations of the active zone lead to sustained changes in neurotransmitter release. Proc Natl Acad Sci U S A. 2010; 107(19):8836-41. PMC: 2889309. DOI: 10.1073/pnas.0906087107. View

5.
Graham M, Burgoyne R . Comparison of cysteine string protein (Csp) and mutant alpha-SNAP overexpression reveals a role for csp in late steps of membrane fusion in dense-core granule exocytosis in adrenal chromaffin cells. J Neurosci. 2000; 20(4):1281-9. PMC: 6772362. View