Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase

Nat Commun. 2014 Jun 30;5:4246. doi: 10.1038/ncomms5246.

Abstract

Phosphorylation has emerged as a crucial regulatory mechanism in the nervous system to integrate the dynamic signalling required for proper synaptic development, function and plasticity, particularly during changes in neuronal activity. Here we present evidence that Minibrain (Mnb; also known as Dyrk1A), a serine/threonine kinase implicated in autism spectrum disorder and Down syndrome, is required presynaptically for normal synaptic growth and rapid synaptic vesicle endocytosis at the Drosophila neuromuscular junction (NMJ). We find that Mnb-dependent phosphorylation of Synaptojanin (Synj) is required, in vivo, for complex endocytic protein interactions and to enhance Synj activity. Neuronal stimulation drives Mnb mobilization to endocytic zones and triggers Mnb-dependent phosphorylation of Synj. Our data identify Mnb as a synaptic kinase that promotes efficient synaptic vesicle recycling by dynamically calibrating Synj function at the Drosophila NMJ, and in turn endocytic capacity, to adapt to conditions of high synaptic activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / enzymology*
  • Drosophila / genetics
  • Drosophila / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Endocytosis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / enzymology
  • Neuromuscular Junction / genetics
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Synapses / enzymology
  • Synaptic Vesicles / enzymology*
  • Synaptic Vesicles / genetics

Substances

  • Drosophila Proteins
  • Nerve Tissue Proteins
  • mnb protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • synaptojanin
  • Phosphoric Monoester Hydrolases