The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone

Fumiko Kawasaki, Janani Iyer, Lisa Lipowski Posey, Chichun E. Sun, Samantha E. Mammen, Huaru Yan, Richard W. Ordway

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18 Citations (Scopus)

Abstract

Members of the DISABLED (DAB) family of proteins are known to play a conserved role in endocytic trafficking of cell surface receptors by functioning as monomeric CLATHRIN-associated sorting proteins that recruit cargo proteins into endocytic vesicles. Here, we report a Drosophila disabled mutant revealing a novel role for DAB proteins in chemical synaptic transmission. This mutant exhibits impaired synaptic function, including a rapid activity-dependent reduction in neurotransmitter release and disruption of synaptic vesicle endocytosis. In presynaptic boutons, Drosophila DAB and CLATHRIN were highly colocalized within two distinct classes of puncta, including relatively dim puncta that were located at active zones and may reflect endocytic mechanisms operating at neurotransmitter release sites. Finally, broader analysis of endocytic proteins, including DYNAMIN, supported a general role for CLATHRIN-mediated endocytic mechanisms in rapid clearance of neurotransmitter release sites for subsequent vesicle priming and refilling of the release-ready vesicle pool.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number25
DOIs
StatePublished - Jun 21 2011

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Synaptic Vesicles
Endocytosis
Neurotransmitter Agents
Drosophila
Proteins
Transport Vesicles
Cell Surface Receptors
Protein Transport
Synaptic Transmission

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone",
abstract = "Members of the DISABLED (DAB) family of proteins are known to play a conserved role in endocytic trafficking of cell surface receptors by functioning as monomeric CLATHRIN-associated sorting proteins that recruit cargo proteins into endocytic vesicles. Here, we report a Drosophila disabled mutant revealing a novel role for DAB proteins in chemical synaptic transmission. This mutant exhibits impaired synaptic function, including a rapid activity-dependent reduction in neurotransmitter release and disruption of synaptic vesicle endocytosis. In presynaptic boutons, Drosophila DAB and CLATHRIN were highly colocalized within two distinct classes of puncta, including relatively dim puncta that were located at active zones and may reflect endocytic mechanisms operating at neurotransmitter release sites. Finally, broader analysis of endocytic proteins, including DYNAMIN, supported a general role for CLATHRIN-mediated endocytic mechanisms in rapid clearance of neurotransmitter release sites for subsequent vesicle priming and refilling of the release-ready vesicle pool.",
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T1 - The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone

AU - Kawasaki, Fumiko

AU - Iyer, Janani

AU - Posey, Lisa Lipowski

AU - Sun, Chichun E.

AU - Mammen, Samantha E.

AU - Yan, Huaru

AU - Ordway, Richard W.

PY - 2011/6/21

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