Delayed reentry of recycling vesicles into the fusion-competent synaptic vesicle pool in synaptojanin 1 knockout mice.
Synaptojanin 1 is a polyphosphoinositide phosphatase implicated in synaptic vesicle recycling. We used FM1-43 imaging and electron microscopy in cultured cortical neurons from control and synaptojanin 1 knockout mice to study how the absence of this protein affects specific steps of the synaptic vesicle cycle. Exoendocytosis after a moderate stimulus was unchanged. However, during prolonged stimulation, the regeneration of fusion-competent synaptic vesicles was severely impaired. In stimulated nerve terminals, there was a persistent accumulation of clathrin-coated vesicles and a backup of newly reformed vesicles in the cytomatrix-rich area around the synaptic vesicle cluster. These findings demonstrate that synaptojanin 1 function is needed for the progression of recycling vesicles to the functional synaptic vesicle pool.
Kim
Warren T
WT
Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
Chang
Sunghoe
S
Daniell
Laurie
L
Cremona
Ottavio
O
Di Paolo
Gilbert
G
De Camilli
Pietro
P
D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D022163:Clathrin-Coated Vesicles / Q000502:physiology; D004705:Endocytosis; D005089:Exocytosis; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*
D009419:Nerve Tissue Proteins; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases