scholarly journals Nicotinamide mononucleotide adenylyltransferase maintains active zone structure by stabilizing Bruchpilot

EMBO Reports ◽  
2012 ◽  
Vol 14 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Shaoyun Zang ◽  
Yousuf O Ali ◽  
Kai Ruan ◽  
R Grace Zhai
Keyword(s):  
Active Zone ◽  
Zone Structure ◽  
Nicotinamide Mononucleotide ◽  
Nicotinamide Mononucleotide Adenylyltransferase

scholarly journals PKC-phosphorylation of Liprin-α3 triggers phase separation and controls presynaptic active zone structure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Javier Emperador-Melero ◽  
Man Yan Wong ◽  
Shan Shan H. Wang ◽  
Giovanni de Nola ◽  
Hajnalka Nyitrai ◽  
...  
Keyword(s):  
Phase Separation ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Hippocampal Neurons ◽  
Phosphorylation Site ◽  
Double Knockout ◽  
Zone Structure ◽  
Presynaptic Nerve Terminal ◽  
Condensate Formation ◽  
And Function

AbstractThe active zone of a presynaptic nerve terminal defines sites for neurotransmitter release. Its protein machinery may be organized through liquid–liquid phase separation, a mechanism for the formation of membrane-less subcellular compartments. Here, we show that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation in transfected HEK293T cells. Condensate formation is triggered by Liprin-α3 PKC-phosphorylation at serine-760, and RIM and Munc13 are co-recruited into membrane-attached condensates. Phospho-specific antibodies establish phosphorylation of Liprin-α3 serine-760 in transfected cells and mouse brain tissue. In primary hippocampal neurons of newly generated Liprin-α2/α3 double knockout mice, synaptic levels of RIM and Munc13 are reduced and the pool of releasable vesicles is decreased. Re-expression of Liprin-α3 restored these presynaptic defects, while mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented this rescue. Finally, PKC activation in these neurons acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. Our findings indicate that PKC-mediated phosphorylation of Liprin-α3 triggers its phase separation and modulates active zone structure and function.

Nicotinamide mononucleotide adenylyltransferase. Molecular and enzymic properties of the homogeneous enzyme from bakers' yeast

Biochemistry ◽  
1986 ◽  
Vol 25 (12) ◽  
pp. 3725-3729 ◽  
Author(s):  
Paolo Natalini ◽  
Silverio Ruggieri ◽  
Nadia Raffaelli ◽  
Giulio Magni
Keyword(s):  
Nicotinamide Mononucleotide ◽  
Nicotinamide Mononucleotide Adenylyltransferase

scholarly journals Identification of the nicotinamide mononucleotide adenylyltransferase of Trypanosoma cruzi

2015 ◽  
Vol 110 (7) ◽  
pp. 890-897 ◽  
Author(s):  
Carlos H Niño ◽  
Nicolás Forero-Baena ◽  
Luis E Contreras ◽  
Diana Sánchez-Lancheros ◽  
Katherine Figarella ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Nicotinamide Mononucleotide ◽  
Nicotinamide Mononucleotide Adenylyltransferase

scholarly journals Phosphorylation triggers presynaptic phase separation of Liprin-α3 to control active zone structure

2020 ◽  
Author(s):  
Javier Emperador-Melero ◽  
Man Yan Wong ◽  
Shan Shan H. Wang ◽  
Giovanni de Nola ◽  
Tom Kirchhausen ◽  
...  
Keyword(s):  
Phase Separation ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Phosphorylation Site ◽  
Double Knockout ◽  
Zone Structure ◽  
And Function ◽  
Pkc Activation ◽  
Liquid Liquid Phase Separation

AbstractLiquid-liquid phase separation enables the assembly of membrane-less subcellular compartments, but testing its biological functions has been difficult. The presynaptic active zone, protein machinery in nerve terminals that defines sites for neurotransmitter release, may be organized through phase separation. Here, we discover that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation upon phosphorylation by PKC at a single site. RIM and Munc13 are co-recruited to membrane-attached condensates, and phospho-specific antibodies establish Liprin-α3 phosphorylation in vivo. At synapses of newly generated Liprin-α2/α3 double knockout mice, RIM, Munc13 and the pool of releasable vesicles were reduced. Re-expression of Liprin-α3 restored these defects, but mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented rescue. Finally, PKC activation acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. We conclude that Liprin-α3 phosphorylation rapidly triggers presynaptic phase separation to modulate active zone structure and function.

Structure and Function of Nicotinamide Mononucleotide Adenylyltransferase

2004 ◽  
Vol 11 (7) ◽  
pp. 873-885 ◽  
Author(s):  
G. Magni ◽  
A. Amici ◽  
M. Emanuelli ◽  
G. Orsomando ◽  
N. Raffaelli ◽  
...  
Keyword(s):  
Structure And Function ◽  
Nicotinamide Mononucleotide ◽  
Nicotinamide Mononucleotide Adenylyltransferase ◽  
And Function

scholarly journals The NAD+ Synthesis Enzyme Nicotinamide Mononucleotide Adenylyltransferase (NMNAT1) Regulates Ribosomal RNA Transcription

2013 ◽  
Vol 288 (29) ◽  
pp. 20908-20917 ◽  
Author(s):  
Tanjing Song ◽  
Leixiang Yang ◽  
Neha Kabra ◽  
Lihong Chen ◽  
John Koomen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Lung Tumor ◽  
Human Cancer ◽  
Rrna Synthesis ◽  
Rrna Transcription ◽  
Nicotinamide Mononucleotide ◽  
Nad Synthesis ◽  
Increased Sensitivity ◽  
Nicotinamide Mononucleotide Adenylyltransferase

The chromosomal region encoding the nuclear NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) is frequently deleted in human cancer. We describe evidence that NMNAT1 interacts with the nucleolar repressor protein nucleomethylin and is involved in regulating rRNA transcription. NMNAT1 binds to nucleomethylin and is recruited into a ternary complex containing the NAD+-dependent deacetylase SirT1. NMNAT1 expression stimulates the deacetylase function of SirT1. Knockdown of NMNAT1 enhances rRNA transcription and promotes cell death after nutrient deprivation. Furthermore, NMNAT1 expression is induced by DNA damage and plays a role in preventing cell death after damage. Heterozygous deletion of NMNAT1 in lung tumor cell lines correlates with low expression level and increased sensitivity to DNA damage. These results suggest that NMNAT1 deletion in tumors may contribute to transformation by increasing rRNA synthesis, but may also increase sensitivity to nutrient stress and DNA damage.

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