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Distinct active zone protein machineries mediate Ca2+ channel clustering and vesicle priming at hippocampal synapses.
Emperador-Melero, Javier; Andersen, Jonathan W; Metzbower, Sarah R; Levy, Aaron D; Dharmasri, Poorna A; de Nola, Giovanni; Blanpied, Thomas A; Kaeser, Pascal S.
Afiliación
  • Emperador-Melero J; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Andersen JW; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Metzbower SR; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Levy AD; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Dharmasri PA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • de Nola G; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Blanpied TA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Kaeser PS; Department of Neurobiology, Harvard Medical School, Boston, MA, USA. kaeser@hms.harvard.edu.
Nat Neurosci ; 27(9): 1680-1694, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39160372
ABSTRACT
Action potentials trigger neurotransmitter release at the presynaptic active zone with spatiotemporal precision. This is supported by protein machinery that mediates synaptic vesicle priming and clustering of CaV2 Ca2+ channels nearby. One model posits that scaffolding proteins directly tether vesicles to CaV2s; however, here we find that at mouse hippocampal synapses, CaV2 clustering and vesicle priming are executed by separate machineries. CaV2 nanoclusters are positioned at variable distances from those of the priming protein Munc13. The active zone organizer RIM anchors both proteins but distinct interaction motifs independently execute these functions. In transfected cells, Liprin-α and RIM form co-assemblies that are separate from CaV2-organizing complexes. At synapses, Liprin-α1-Liprin-α4 knockout impairs vesicle priming but not CaV2 clustering. The cell adhesion protein PTPσ recruits Liprin-α, RIM and Munc13 into priming complexes without co-clustering CaV2s. We conclude that active zones consist of distinct machineries to organize CaV2s and prime vesicles, and Liprin-α and PTPσ specifically support priming site assembly.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Vesículas Sinápticas / Hipocampo Límite: Animals Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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 / Vesículas Sinápticas / Hipocampo Límite: Animals Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos