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Collybistin SH3-protein isoforms are expressed in the rat brain promoting gephyrin and GABA-A receptor clustering at GABAergic synapses.
George, Shanu; Bear, John; Taylor, Michael J; Kanamalla, Karthik; Fekete, Christopher D; Chiou, Tzu-Ting; Miralles, Celia P; Papadopoulos, Theofilos; De Blas, Angel L.
Afiliación
  • George S; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Bear J; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Taylor MJ; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Kanamalla K; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Fekete CD; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Chiou TT; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Miralles CP; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
  • Papadopoulos T; Department of Molecular Biology, Universitätsmedizin Göttingen, Göttingen, Germany.
  • De Blas AL; Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
J Neurochem ; 157(4): 1032-1051, 2021 05.
Article en En | MEDLINE | ID: mdl-33316079
Collybistin (CB) is a guanine nucleotide exchange factor (GEF) selectively localized at GABAergic and glycinergic postsynapses. Analysis of mRNA shows that several isoforms of collybistin are expressed in the brain. Some of the isoforms have a SH3 domain (CBSH3+) and some have no SH3 domain (CBSH3-). The CBSH3+ mRNAs are predominantly expressed over CBSH3-. However, in an immunoblot study of mouse brain homogenates, only CBSH3+ protein isoforms were detected, proposing that CBSH3- protein might not be expressed in the brain. The expression or lack of expression of CBSH3- protein is an important issue because CBSH3- has a strong effect in promoting the postsynaptic clustering of gephyrin and GABA-A receptors (GABAA Rs). Moreover CBSH3- is constitutively active; therefore lower expression of CBSH3- protein might play a relatively stronger functional role than the more abundant but self-inhibited CBSH3+ isoforms, which need to be activated. We are now showing that: (a) CBSH3- protein is expressed in the brain; (b) parvalbumin positive (PV+) interneurons show higher expression of CBSH3- protein than other neurons; (c) CBSH3- is associated with GABAergic synapses in various regions of the brain and (d) knocking down CBSH3- in hippocampal neurons decreases the synaptic clustering of gephyrin and GABAA Rs. The results show that CBSH3- protein is expressed in the brain and that it plays a significant role in the size regulation of the GABAergic postsynapse.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Encéfalo / Receptores de GABA-A / Factores de Intercambio de Guanina Nucleótido Rho / Proteínas de la Membrana Límite: Animals Idioma: En Revista: J Neurochem Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Encéfalo / Receptores de GABA-A / Factores de Intercambio de Guanina Nucleótido Rho / Proteínas de la Membrana Límite: Animals Idioma: En Revista: J Neurochem Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido