FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development.
Neuron
; 73(5): 903-10, 2012 Mar 08.
Article
en En
| MEDLINE
| ID: mdl-22405201
ABSTRACT
Latrophilins (LPHNs) are a small family of G protein-coupled receptors known to mediate the massive synaptic exocytosis caused by the black widow spider venom α-latrotoxin, but their endogenous ligands and function remain unclear. Mutations in LPHN3 are strongly associated with attention deficit hyperactivity disorder, suggesting a role for latrophilins in human cognitive function. Using affinity chromatography and mass spectrometry, we identify the FLRT family of leucine-rich repeat transmembrane proteins as endogenous postsynaptic ligands for latrophilins. We demonstrate that the FLRT3 and LPHN3 ectodomains interact with high affinity in trans and that interference with this interaction using soluble recombinant LPHN3, LPHN3 shRNA, or FLRT3 shRNA reduces excitatory synapse density in cultured neurons. In addition, reducing FLRT3 levels with shRNA in vivo decreases afferent input strength and dendritic spine number in dentate granule cells. These observations indicate that LPHN3 and its ligand FLRT3 play an important role in glutamatergic synapse development.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinapsis
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Receptores de Péptidos
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Potenciales Postsinápticos Excitadores
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Receptores Acoplados a Proteínas G
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Proteínas de la Membrana
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Neuronas
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos