SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development.
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.
Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
Evgenia
E
Kalashnikova
Ramón A
RA
Lorca
Inderpreet
I
Kaur
Gustavo A
GA
Barisone
Bonnie
B
Li
Tatsuto
T
Ishimaru
James S
JS
Trimmer
Durga P
DP
Mohapatra
Elva
E
Díaz
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C547920:SynDIG1 protein, rat