Functional properties of multiple synaptotagmins in brain.
At least four forms of synaptotagmin are expressed in neurons. Of these, synaptotagmin I has an essential function in mediating Ca(2+)-triggered neurotransmitter release at hippocampal synapses, but the functional implications of multiple synaptotagmins are unknown. Synaptotagmins I-III exhibit a strikingly differential distribution between synapses, with most neurons coexpressing either synaptotagmins I or II with III. Synaptotagmin IV is present uniformly throughout the brain at low levels. Synaptotagmins III and IV are both coexpressed with synaptotagmin I in hippocampal synapses, suggesting that these synaptotagmins are not functionally redundant. The first C2 domains of synaptotagmins I-III exhibit similar Ca2+ affinities in phospholipid-binding assays, whereas that of synaptotagmin IV is unable to bind Ca2+. All synaptotagmins tested bind the clathrin-adaptor protein AP-2 with high affinity. Our results suggest that different synaptotagmins serve distinct but overlapping functions in neuronal membrane traffic, with synaptotagmins I and II representing alternative Ca2+ sensors in exocytosis and all synaptotagmins functioning as AP-2 receptors in endocytosis.
Ullrich
B
B
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Li
C
C
Zhang
J Z
JZ
McMahon
H
H
Anderson
R G
RG
Geppert
M
M
Südhof
T C
TC
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013569:Synapses / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins
D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D010743:Phospholipids; D010750:Phosphoproteins; D012333:RNA, Messenger; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; C494294:Syt4 protein, rat; D050857:Synaptotagmins; D002118:Calcium