Your browser doesn't support javascript.
loading
Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex.
Sugiura, Hiroko; Yasuda, Shin; Katsurabayashi, Shutaro; Kawano, Hiroyuki; Endo, Kentaro; Takasaki, Kotaro; Iwasaki, Katsunori; Ichikawa, Masumi; Kobayashi, Toshiyuki; Hino, Okio; Yamagata, Kanato.
Afiliación
  • Sugiura H; Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
  • Yasuda S; Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
  • Katsurabayashi S; Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
  • Kawano H; Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
  • Endo K; Center of Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
  • Takasaki K; Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
  • Iwasaki K; Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
  • Ichikawa M; Center of Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
  • Kobayashi T; Department of Pathology and Oncology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
  • Hino O; Department of Pathology and Oncology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
  • Yamagata K; Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Nat Commun ; 6: 6842, 2015 Apr 16.
Article en En | MEDLINE | ID: mdl-25880340
Rheb is a small GTP-binding protein and its GTPase activity is activated by the complex of Tsc1 and Tsc2 whose mutations cause tuberous sclerosis complex (TSC). We previously reported that cultured TSC neurons showed impaired spine synapse morphogenesis in an mTORC1-independent manner. Here we show that the PDZ protein syntenin preferentially binds to the GDP-bound form of Rheb. The levels of syntenin are significantly higher in TSC neurons than in wild-type neurons because the Rheb-GDP-syntenin complex is prone to proteasomal degradation. Accumulated syntenin in TSC neurons disrupts spine synapse formation through inhibition of the association between syndecan-2 and calcium/calmodulin-dependent serine protein kinase. Instead, syntenin enhances excitatory shaft synapse formation on dendrites by interacting with ephrinB3. Downregulation of syntenin in TSC neurons restores both spine and shaft synapse densities. These findings suggest that Rheb-syntenin signalling may be a novel therapeutic target for abnormalities in spine and shaft synapses in TSC neurons.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Esclerosis Tuberosa / Neuropéptidos / Proteínas de Unión al GTP Monoméricas / Espinas Dendríticas / Sinteninas / Neuronas Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Esclerosis Tuberosa / Neuropéptidos / Proteínas de Unión al GTP Monoméricas / Espinas Dendríticas / Sinteninas / Neuronas Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido