The LGI1–ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function
Copyright policy )The LGI1–ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function
Significance The PSD-95 family proteins serve as central scaffolds of excitatory synapses. Their expression levels dictate synaptic strength, and the functions of many synaptic organizing molecules are dependent on interactions with these proteins. Yet, it is unclear what guides PSD-95 into maturing synapses, which occurs postnatally and is required for proper synapse development. Here, we establish that the secreted protein LGI1 controls the functional incorporation of PSD-95 through interactions with the transmembrane protein ADAM22. This process occurs in a paracrine fashion, with LGI1 released from the pre- and postsynaptic cell able to modulate postsynaptic strength. Our data illustrate a previously undescribed level of synaptic organization, identifying a critical role for the LGI1–ADAM22 complex in controlling the function of PSD-95 itself and, in turn, normal synapse development.
Protein Structure, 1.1 Normal biological development and functioning, Knockout, Amino Acid Motifs, ADAM22, Nerve Tissue Proteins, Synaptic Transmission, Mice, Underpinning research, Animals, PSD-95, Electrodes, Mice, Knockout, Neurons, Cell Membrane, Neurosciences, Intracellular Signaling Peptides and Proteins, Brain, Membrane Proteins, Proteins, Brain Disorders, Protein Structure, Tertiary, ADAM Proteins, Phenotype, Gene Expression Regulation, Neurological, Synapses, synaptic organization, LGI1, synapse development, Disks Large Homolog 4 Protein, Guanylate Kinases, Tertiary, Protein Binding
Protein Structure, 1.1 Normal biological development and functioning, Knockout, Amino Acid Motifs, ADAM22, Nerve Tissue Proteins, Synaptic Transmission, Mice, Underpinning research, Animals, PSD-95, Electrodes, Mice, Knockout, Neurons, Cell Membrane, Neurosciences, Intracellular Signaling Peptides and Proteins, Brain, Membrane Proteins, Proteins, Brain Disorders, Protein Structure, Tertiary, ADAM Proteins, Phenotype, Gene Expression Regulation, Neurological, Synapses, synaptic organization, LGI1, synapse development, Disks Large Homolog 4 Protein, Guanylate Kinases, Tertiary, Protein Binding
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