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PMID:16186258

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Citation

Olsen, O, Moore, KA, Fukata, M, Kazuta, T, Trinidad, JC, Kauer, FW, Streuli, M, Misawa, H, Burlingame, AL, Nicoll, RA and Bredt, DS (2005) Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex. J. Cell Biol. 170:1127-34

Abstract

Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli-CASK-Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic adhesion molecules to the cytoskeleton. In this study, we purified the MALS protein complex from brain and found liprin-alpha as a major component. Liprin proteins organize the presynaptic active zone and regulate neurotransmitter release. Fittingly, mutant mice lacking all three MALS isoforms died perinatally with difficulty breathing and impaired excitatory synaptic transmission. Excitatory postsynaptic currents were dramatically reduced in autaptic cultures from MALS triple knockout mice due to a presynaptic deficit in vesicle cycling. These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone.

Links

PubMed PMC2171538 Online version:10.1083/jcb.200503011

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cells, Cultured; Female; Gene Targeting; Macromolecular Substances/metabolism; Male; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Knockout; Neurons/physiology; Neurotransmitter Agents/metabolism; Particle Size; Patch-Clamp Techniques; Presynaptic Terminals/metabolism; Proteomics; Synaptic Transmission/genetics; Two-Hybrid System Techniques; Vesicular Transport Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:APBA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:B2RXQ2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:B2RXW8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:B8QI33

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:CSKP

located_in

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:LIN7B

acts_upstream_of_or_within

GO:0007269: neurotransmitter secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1330839
MGI:MGI:2135609

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:LIN7C

located_in

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:LIN7C

acts_upstream_of_or_within

GO:0007269: neurotransmitter secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1330858
MGI:MGI:2135609

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:Q3UJC0

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:LIPA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BSS9

F

Seeded From UniProt

complete

MOUSE:LIPA2

located_in

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:LIN7A

acts_upstream_of_or_within

GO:0007269: neurotransmitter secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1330839
MGI:MGI:2135609

P

Seeded From UniProt

complete

MOUSE:S4R1D4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:S4R1I7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O88952

F

Seeded From UniProt

complete

MOUSE:CSKP

part_of

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(EMAPA:16894)

Seeded From UniProt

complete

See also

References

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