scholarly journals N-glycosylation requirements in neuromuscular synaptogenesis

Development ◽  
2013 ◽  
Vol 140 (24) ◽  
pp. 4970-4981 ◽  
Author(s):  
W. Parkinson ◽  
M. L. Dear ◽  
E. Rushton ◽  
K. Broadie
Keyword(s):  
Neuromuscular Synaptogenesis

scholarly journals Regulation of SH3PX1 by dNedd4-long at the Drosophila neuromuscular junction

2018 ◽  
Vol 294 (5) ◽  
pp. 1739-1752 ◽  
Author(s):  
Samantha S. Wasserman ◽  
Alina Shteiman-Kotler ◽  
Kathryn Harris ◽  
Konstantin G. Iliadi ◽  
Avinash Persaud ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Neuromuscular Junctions ◽  
Cell Periphery ◽  
Middle Region ◽  
Binding Partners ◽  
Direct Binding ◽  
Specific Regulation ◽  
Neuromuscular Synaptogenesis

Drosophila Nedd4 (dNedd4) is a HECT E3 ubiquitin ligase present in two major isoforms: short (dNedd4S) and long (dNedd4Lo), with the latter containing two unique regions (N terminus and Middle). Although dNedd4S promotes neuromuscular synaptogenesis (NMS), dNedd4Lo inhibits it and impairs larval locomotion. To explain how dNedd4Lo inhibits NMS, MS analysis was performed to find its binding partners and identified SH3PX1, which binds dNedd4Lo unique Middle region. SH3PX1 contains SH3, PX, and BAR domains and is present at neuromuscular junctions, where it regulates active zone ultrastructure and presynaptic neurotransmitter release. Here, we demonstrate direct binding of SH3PX1 to the dNedd4Lo Middle region (which contains a Pro-rich sequence) in vitro and in cells, via the SH3PX1-SH3 domain. In Drosophila S2 cells, dNedd4Lo overexpression reduces SH3PX1 levels at the cell periphery. In vivo overexpression of dNedd4Lo post-synaptically, but not pre-synaptically, reduces SH3PX1 levels at the subsynaptic reticulum and impairs neurotransmitter release. Unexpectedly, larvae that overexpress dNedd4Lo post-synaptically and are heterozygous for a null mutation in SH3PX1 display increased neurotransmission compared with dNedd4Lo or SH3PX1 mutant larvae alone, suggesting a compensatory effect from the remaining SH3PX1 allele. These results suggest a post-synaptic–specific regulation of SH3PX1 by dNedd4Lo.

Neuromuscular synaptogenesis: coordinating partners with multiple functions

2014 ◽  
Vol 15 (11) ◽  
pp. 703-718 ◽  
Author(s):  
Houssam Darabid ◽  
Anna P. Perez-Gonzalez ◽  
Richard Robitaille
Keyword(s):  
Multiple Functions ◽  
Neuromuscular Synaptogenesis

Defective neuromuscular synaptogenesis in mice expressing constitutively active ErbB2 in skeletal muscle fibers

2006 ◽  
Vol 31 (2) ◽  
pp. 334-345 ◽  
Author(s):  
Olga N. Ponomareva ◽  
Hualong Ma ◽  
Vita M. Vock ◽  
Elaine L. Ellerton ◽  
Susan E. Moody ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibers ◽  
Skeletal Muscle Fibers ◽  
Neuromuscular Synaptogenesis ◽  
Constitutively Active

scholarly journals Aberrant Morphology and Residual Transmitter Release at the Munc13-Deficient Mouse Neuromuscular Synapse

2005 ◽  
Vol 25 (14) ◽  
pp. 5973-5984 ◽  
Author(s):  
Frédérique Varoqueaux ◽  
Michèle S. Sons ◽  
Jaap J. Plomp ◽  
Nils Brose
Keyword(s):  
Neuromuscular Junction ◽  
Synaptic Vesicle ◽  
Motor Neurons ◽  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Neuromuscular Junctions ◽  
Neuromuscular Synapse ◽  
Synaptic Activity ◽  
Neuromuscular Synaptogenesis ◽  
Deficient Mice

ABSTRACT In cultured hippocampal neurons, synaptogenesis is largely independent of synaptic transmission, while several accounts in the literature indicate that synaptogenesis at cholinergic neuromuscular junctions in mammals appears to partially depend on synaptic activity. To systematically examine the role of synaptic activity in synaptogenesis at the neuromuscular junction, we investigated neuromuscular synaptogenesis and neurotransmitter release of mice lacking all synaptic vesicle priming proteins of the Munc13 family. Munc13-deficient mice are completely paralyzed at birth and die immediately, but form specialized neuromuscular endplates that display typical synaptic features. However, the distribution, number, size, and shape of these synapses, as well as the number of motor neurons they originate from and the maturation state of muscle cells, are profoundly altered. Surprisingly, Munc13-deficient synapses exhibit significantly increased spontaneous quantal acetylcholine release, although fewer fusion-competent synaptic vesicles are present and nerve stimulation-evoked secretion is hardly elicitable and strongly reduced in magnitude. We conclude that the residual transmitter release in Munc13-deficient mice is not sufficient to sustain normal synaptogenesis at the neuromuscular junction, essentially causing morphological aberrations that are also seen upon total blockade of neuromuscular transmission in other genetic models. Our data confirm the importance of Munc13 proteins in synaptic vesicle priming at the neuromuscular junction but indicate also that priming at this synapse may differ from priming at glutamatergic and γ-aminobutyric acid-ergic synapses and is partly Munc13 independent. Thus, non-Munc13 priming proteins exist at this synapse or vesicle priming occurs in part spontaneously: i.e., without dedicated priming proteins in the release machinery.

Commissureless endocytosis is correlated with initiation of neuromuscular synaptogenesis

Development ◽  
1998 ◽  
Vol 125 (19) ◽  
pp. 3853-3863 ◽  
Author(s):  
B. Wolf ◽  
M.A. Seeger ◽  
A. Chiba
Keyword(s):  
Cell Surface ◽  
Transmembrane Protein ◽  
Muscle Cells ◽  
Growth Cones ◽  
Drosophila Embryo ◽  
Loss Of Function ◽  
Wild Type ◽  
Dynamic Cell ◽  
Neuromuscular Synaptogenesis ◽  
Surface Remodeling

We show that the Commissureless (COMM) transmembrane protein is required at neuromuscular synaptogenesis. All muscles in the Drosophila embryo express COMM during the period of motoneuron-muscle interaction. It is endocytosed into muscles before synaptogenesis. In comm loss-of-function mutants, motoneuron growth cones fail to initiate synaptogenesis at target muscles. This stall phenotype is rescued by supplying wild-type COMM to the muscles. Cytoplasmically truncated COMM protein fails to internalize. Expressing this mutant protein in muscles phenocopies the synaptogenesis defects of comm mutants. Thus, synaptogenesis initiation is positively correlated with endocytosis of COMM in postsynaptic muscle cells. We propose that COMM is an essential part of the dynamic cell surface remodeling needed by postsynaptic cells in coordinating synaptogenesis initiation.

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