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PMID:20152115

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Citation

Kalashnikova, E, Lorca, RA, Kaur, I, Barisone, GA, Li, B, Ishimaru, T, Trimmer, JS, Mohapatra, DP and Díaz, E (2010) SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development. Neuron 65:80-93

Abstract

During development of the central nervous system, precise synaptic connections between presynaptic and postsynaptic neurons are formed. While significant progress has been made in our understanding of AMPA receptor trafficking during synaptic plasticity, less is known about the molecules that recruit AMPA receptors to nascent synapses during synaptogenesis. Here we identify a type II transmembrane protein (SynDIG1) that regulates AMPA receptor content at developing synapses in dissociated rat hippocampal neurons. SynDIG1 colocalizes with AMPA receptors at synapses and at extrasynaptic sites and associates with AMPA receptors in heterologous cells and brain. Altered levels of SynDIG1 in cultured neurons result in striking changes in excitatory synapse number and function. SynDIG1-mediated synapse development is dependent on association with AMPA receptors via its extracellular C terminus. Intriguingly, SynDIG1 content in dendritic spines is regulated by neuronal activity. Altogether, we define SynDIG1 as an activity-regulated transmembrane protein that regulates excitatory synapse development.

Links

PubMed PMC2822728 Online version:10.1016/j.neuron.2009.12.021

Keywords

Amino Acid Sequence; Animals; Cell Line; Excitatory Postsynaptic Potentials/physiology; Female; Gene Expression Regulation; Hippocampus/cytology; Humans; Membrane Proteins/genetics; Membrane Proteins/metabolism; Molecular Sequence Data; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/cytology; Neurons/physiology; Patch-Clamp Techniques; Pregnancy; Rats; Receptors, AMPA/genetics; Receptors, AMPA/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Synapses/physiology; Synapses/ultrastructure

Significance

Annotations

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

MOUSE:SYNG1

enables

GO:0035254: glutamate receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P23819

F

Seeded From UniProt

complete

MOUSE:SYNG1

enables

GO:0035254: glutamate receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P23818

F

Seeded From UniProt

complete

MOUSE:SYNG1

NOT|located_in

GO:0000139: Golgi membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SYNG1

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SYNG1

involved_in

GO:0006886: intracellular protein transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SYNG1

enables

GO:0042803: protein homodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SYNG1

involved_in

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SYNG1

located_in

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SYNG1

located_in

GO:0031901: early endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GRIA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A2ANU3

F

Seeded From UniProt

complete

MOUSE:GRIA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A2ANU3

F

Seeded From UniProt

complete

RAT:SYNG1

located_in

GO:0060076: excitatory synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SYNG1

located_in

GO:0043197: dendritic spine

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SYNG1

located_in

GO:0043198: dendritic shaft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SYNG1

located_in

GO:0044297: cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SYNG1

involved_in

GO:0051965: positive regulation of synapse assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SYNG1

involved_in

GO:0097091: synaptic vesicle clustering

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SYNG1

involved_in

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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