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PMID:19628693

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Citation

Wittenmayer, N, Körber, C, Liu, H, Kremer, T, Varoqueaux, F, Chapman, ER, Brose, N, Kuner, T and Dresbach, T (2009) Postsynaptic Neuroligin1 regulates presynaptic maturation. Proc. Natl. Acad. Sci. U.S.A. 106:13564-9

Abstract

Presynaptic nerve terminals pass through distinct stages of maturation after their initial assembly. Here we show that the postsynaptic cell adhesion molecule Neuroligin1 regulates key steps of presynaptic maturation. Presynaptic terminals from Neuroligin1-knockout mice remain structurally and functionally immature with respect to active zone stability and synaptic vesicle pool size, as analyzed in cultured hippocampal neurons. Conversely, overexpression of Neuroligin1 in immature neurons, that is within the first 5 days after plating, induced the formation of presynaptic boutons that had hallmarks of mature boutons. In particular, Neuroligin1 enhanced the size of the pool of recycling synaptic vesicles, the rate of synaptic vesicle exocytosis, the fraction of boutons responding to depolarization, as well as the responsiveness of the presynaptic release machinery to phorbol ester stimulation. Moreover, Neuroligin1 induced the formation of active zones that remained stable in the absence of F-actin, another hallmark of advanced maturation. Acquisition of F-actin independence of the active zone marker Bassoon during culture development or induced via overexpression of Neuroligin1 was activity-dependent. The extracellular domain of Neuroligin1 was sufficient to induce assembly of functional presynaptic terminals, while the intracellular domain was required for terminal maturation. These data show that induction of presynaptic terminal assembly and maturation involve mechanistically distinct actions of Neuroligins, and that Neuroligin1 is essential for presynaptic terminal maturation.

Links

PubMed PMC2726414 Online version:10.1073/pnas.0905819106

Keywords

Actins/metabolism; Animals; Cell Adhesion Molecules, Neuronal; Green Fluorescent Proteins/metabolism; Mice; Nerve Tissue Proteins/metabolism; Neural Cell Adhesion Molecules/chemistry; Neural Cell Adhesion Molecules/metabolism; Presynaptic Terminals/metabolism; Protein Structure, Tertiary; Rats; Rats, Wistar; Recombinant Fusion Proteins/metabolism; Synaptic Potentials/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:NLGN1

involved_in

GO:2000302: positive regulation of synaptic vesicle exocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0048789: cytoskeletal matrix organization at active zone

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0072553: terminal button organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

GO:0097105: presynaptic membrane assembly

ECO:0000315:

P

To investigate maturation of presynaptic bouton, presynaptic markers were used Basson. Figure 1 shows increase in Basson expression when hippocampal neurons were transfected with over expression of Nlgn1, by 2.3 fold, figure 1. Similar result are seen in figure 4G, SV (synaptic vesicle) recycling was impaired when Nlgn1 is mutated. SV trafficking is part of presynaptic maturation.

complete
CACAO 3155

RAT:NLGN1

GO:0051968: positive regulation of synaptic transmission, glutamatergic

ECO:0000315:

P

Figure 4A, B showed increase mini frequency in Nlgn1 overexpression compared to non-transfected cells. Figure 4C and D, when NMDA receptors blocker is used EPSC amplitude was decrease.

complete
CACAO 3156

RAT:NLGN1

GO:2000463: positive regulation of excitatory postsynaptic membrane potential

ECO:0000315:

P

Figure 4C and D, when NMDA receptors blocker is used EPSC amplitude was decreased.

complete
CACAO 3157

RAT:NLGN1

GO:2000310: regulation of N-methyl-D-aspartate selective glutamate receptor activity

ECO:0000315:

P

Figure 4C and D, when NMDA receptors blocker is used EPSC amplitude was decreased.

complete
CACAO 3158

RAT:NLGN1

GO:0048489: synaptic vesicle transport

ECO:0000315:

P

Figure 4G, SV (synaptic vesicle) recycling was impaired when Nlgn1 is mutated. SV trafficking is part of presynaptic maturation. Over expression of Nlgn1 increased SV at bouton figure 4F.

complete
CACAO 3159

RAT:NLGN1

GO:0097091: synaptic vesicle clustering

ECO:0000315:

P

Figure S3 increased synaptic vesicle clustering to synapse when Nlgn1 over expressed

complete
CACAO 3160

RAT:NLGN1

involved_in

GO:1900244: positive regulation of synaptic vesicle endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0051968: positive regulation of synaptic transmission, glutamatergic

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:2000463: positive regulation of excitatory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:2000310: regulation of NMDA receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0048489: synaptic vesicle transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0097091: synaptic vesicle clustering

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

involved_in

GO:2000302: positive regulation of synaptic vesicle exocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

involved_in

GO:1900244: positive regulation of synaptic vesicle endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

involved_in

GO:0072553: terminal button organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

involved_in

GO:0048789: cytoskeletal matrix organization at active zone

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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