PMID- 10575017
OWN - NLM
STAT- MEDLINE
DCOM- 19991217
LR  - 20191023
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 23
DP  - 1999 Dec 1
TI  - A role for the clathrin assembly domain of AP180 in synaptic vesicle endocytosis.
PG  - 10201-12
AB  - We have used the squid giant synapse to determine whether clathrin assembly by
      AP180 is important for synaptic vesicle endocytosis. The squid homolog of AP180
      encodes a 751 amino acid protein with 40% sequence identity to mouse AP180.
      Alignment of squid AP180 with other AP180 homologs shows that amino acid identity
      was highest in the N-terminal inositide-binding domain of the protein and weakest
      in the C-terminal clathrin assembly domain. Recombinant squid AP180 was able to
      assemble clathrin in vitro, suggesting a conserved three-dimensional structure
      that mediates clathrin assembly despite the divergent primary sequence of the
      C-terminal domain. Microinjection of the C-terminal domains of either mouse or
      squid AP180 into the giant presynaptic terminal of squid enhanced synaptic
      transmission. Conversely, a peptide from the C-terminal domain of squid AP180
      that inhibited clathrin assembly in vitro completely blocked synaptic
      transmission when it was injected into the giant presynaptic terminal. This
      inhibitory effect occurred over a time scale of minutes when the synapse was
      stimulated at low (0.03 Hz), physiological rates. Electron microscopic analysis
      revealed several structural changes consistent with the inhibition of synaptic
      vesicle endocytosis; peptide-injected terminals had far fewer synaptic vesicles, 
      were depleted of coated vesicles, and had a larger plasma membrane perimeter than
      terminals injected with control solutions. In addition, the remaining synaptic
      vesicles were significantly larger in diameter. We conclude that the clathrin
      assembly domain of AP180 is important for synaptic vesicle recycling at
      physiological rates of activity and that assembly of clathrin by AP180 is
      necessary for maintaining a pool of releasable synaptic vesicles.
FAU - Morgan, J R
AU  - Morgan JR
AD  - Department of Neurobiology, Duke University Medical Center, Durham, North
      Carolina 27710, USA.
FAU - Zhao, X
AU  - Zhao X
FAU - Womack, M
AU  - Womack M
FAU - Prasad, K
AU  - Prasad K
FAU - Augustine, G J
AU  - Augustine GJ
FAU - Lafer, E M
AU  - Lafer EM
LA  - eng
SI  - GENBANK/AF182339
SI  - GENBANK/AF182340
GR  - R01 NS029051/NS/NINDS NIH HHS/United States
GR  - NS21624/NS/NINDS NIH HHS/United States
GR  - NS29051/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Monomeric Clathrin Assembly Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (clathrin assembly protein AP180)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Cloning, Molecular
MH  - Decapodiformes
MH  - Endocytosis/*physiology
MH  - Molecular Sequence Data
MH  - *Monomeric Clathrin Assembly Proteins
MH  - Nerve Tissue Proteins/*genetics/*physiology
MH  - Phosphoproteins/*genetics/*physiology
MH  - Sequence Homology, Amino Acid
MH  - Synaptic Transmission/physiology
MH  - Synaptic Vesicles/*physiology
PMC - PMC6782422
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Dec 1;19(23):10201-12.