Calcineurin is universally involved in vesicle endocytosis at neuronal and nonneuronal secretory cells.
Calcium influx triggers and accelerates endocytosis in nerve terminals and nonneuronal secretory cells. Whether calcium/calmodulin-activated calcineurin, which dephosphorylates endocytic proteins, mediates this process is highly controversial for different cell types, developmental stages, and endocytic forms. Using three preparations that previously produced discrepant results (i.e., large calyx-type synapses, conventional cerebellar synapses, and neuroendocrine chromaffin cells containing large dense-core vesicles), we found that calcineurin gene knockout consistently slowed down endocytosis, regardless of cell type, developmental stage, or endocytic form (rapid or slow). In contrast, calcineurin and calmodulin blockers slowed down endocytosis at a relatively small calcium influx, but did not inhibit endocytosis at a large calcium influx, resulting in false-negative results. These results suggest that calcineurin is universally involved in endocytosis. They may also help explain the discrepancies among previous pharmacological studies. We therefore suggest that calcineurin should be included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis.
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Xin-Sheng
XS
Wu
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Zhen
Z
Zhang
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Wei-Dong
WD
Zhao
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Dongsheng
D
Wang
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Fujun
F
Luo
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. Electronic address: wul@ninds.nih.gov.
Ling-Gang
LG
Wu
D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism*; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
D019703:Calcineurin