Intersectin is a negative regulator of dynamin recruitment to the synaptic endocytic zone in the central synapse.
Intersectin is a multidomain dynamin-binding protein implicated in numerous functions in the nervous system, including synapse formation and endocytosis. Here, we demonstrate that during neurotransmitter release in the central synapse, intersectin, like its binding partner dynamin, is redistributed from the synaptic vesicle pool to the periactive zone. Acute perturbation of the intersectin-dynamin interaction by microinjection of either intersectin antibodies or Src homology 3 (SH3) domains inhibited endocytosis at the fission step. Although the morphological effects induced by the different reagents were similar, antibody injections resulted in a dramatic increase in dynamin immunoreactivity around coated pits and at constricted necks, whereas synapses microinjected with the GST (glutathione S-transferase)-SH3C domain displayed reduced amounts of dynamin in the neck region. Our data suggest that intersectin controls the amount of dynamin released from the synaptic vesicle cluster to the periactive zone and that it may regulate fission of clathrin-coated intermediates.
Evergren
Emma
E
Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Gad
Helge
H
Walther
Kristin
K
Sundborger
Anna
A
Tomilin
Nikolay
N
Shupliakov
Oleg
O
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000502:physiology / Q000648:ultrastructure; D007798:Lampreys; D008969:Molecular Sequence Data; D009433:Neural Inhibition / Q000502:physiology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000502:physiology* / Q000648:ultrastructure
D033942:Adaptor Proteins, Vesicular Transport; C115919:intersectin 1; D034281:Dynamins