Synaptic localization and activity of ADAM10 regulate excitatory synapses through N-cadherin cleavage.
N-Cadherin has an important role during dendrite arborization, axon guidance, and synaptogenesis. In particular, at synaptic sites, N-cadherin is involved in the regulation of cell-cell adhesion and in morphology and plasticity control. Recent studies have shown that N-cadherin can be cleaved by the metalloproteinase ADAM10. Here we demonstrate that impairing ADAM10 localization and activity at synaptic sites decreases its processing of N-cadherin. This leads to an accumulation of the full-length form of N-cadherin, to an increase in spine head width, and to modifications of the number and function of glutamate receptors of AMPA type, both in vitro and in vivo. Our results indicate a key role for ADAM10 in the complex sequence of events through which N-cadherin affects spine maturation and controls structure and function of glutamatergic synapses.
Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy.
Matteo
M
Malinverno
Mario
M
Carta
Roberta
R
Epis
Elena
E
Marcello
Chiara
C
Verpelli
Flaminio
F
Cattabeni
Carlo
C
Sala
Christophe
C
Mulle
Monica
M
Di Luca
Fabrizio
F
Gardoni
D051722:ADAM Proteins / Q000032:analysis / Q000502:physiology*; D000072197:ADAM10 Protein; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000032:analysis / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D015820:Cadherins / Q000502:physiology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D018698:Glutamic Acid / Q000737:chemistry / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D013569:Synapses / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D008565:Membrane Proteins; D018698:Glutamic Acid; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human