GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20410104

From GONUTS
Jump to: navigation, search
Citation

Lee, HW, Kim, Y, Han, K, Kim, H and Kim, E (2010) The phosphoinositide 3-phosphatase MTMR2 interacts with PSD-95 and maintains excitatory synapses by modulating endosomal traffic. J. Neurosci. 30:5508-18

Abstract

MTMR2 is a 3-phosphatase specific for the phosphoinositides PI(3)P and PI(3,5)P(2), which are mainly present on endosomes. Mutations in the MTMR2 gene in Schwann cells lead to a severe demyelinating peripheral neuropathy known as Charcot-Marie-Tooth disease type 4B1. MTMR2 expression is also detected in peripheral and central neurons, but neural functions of MTMR2 remain unclear. Here, we report that MTMR2 is localized to excitatory synapses of central neurons via direct interaction with PSD-95, a postsynaptic scaffolding protein abundant at excitatory synapses. Knockdown of MTMR2 in cultured neurons markedly reduces excitatory synapse density and function. This effect is rescued by wild-type MTMR2 but not by a mutant MTMR2 lacking PSD-95 binding or 3-phosphatase activity. MTMR2 knockdown leads to a decrease in the intensity of EEA1-positive early endosomes in dendrites but increases the intensity in the cell body region. Moreover, MTMR2 suppression promotes endocytosis, but not recycling, of the GluR2 subunit of AMPA receptors, which is an endosomal cargo. In addition, colocalization of internalized GluR2 with Lamp1-positive late endosomes/lysosomes is enhanced in the cell body area but not in dendrites. These results suggest that PSD-95-interacting MTMR2 contributes to the maintenance of excitatory synapses by inhibiting excessive endosome formation and destructive endosomal traffic to lysosomes.

Links

PubMed Online version:10.1523/JNEUROSCI.4283-09.2010

Keywords

Animals; Cell Line; Cells, Cultured; Endosomes/enzymology; Endosomes/metabolism; Endosomes/pathology; Excitatory Postsynaptic Potentials/physiology; Gene Knockdown Techniques; Hippocampus/enzymology; Hippocampus/metabolism; Hippocampus/pathology; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Intracellular Signaling Peptides and Proteins/physiology; Lysosomes/enzymology; Lysosomes/physiology; Membrane Proteins/metabolism; Membrane Proteins/physiology; Neural Inhibition; Phosphoric Monoester Hydrolases/metabolism; Phosphoric Monoester Hydrolases/physiology; Protein Binding/physiology; Protein Transport/physiology; Protein Tyrosine Phosphatases, Non-Receptor/metabolism; Protein Tyrosine Phosphatases, Non-Receptor/physiology; Rats; Synapses/enzymology; Synapses/physiology

Significance

Annotations

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

RAT:D3ZA31

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q62936

F

Seeded From UniProt

complete

RAT:D3ZA31

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q63622

F

Seeded From UniProt

complete

RAT:D3ZA31

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31016

F

Seeded From UniProt

complete

RAT:D3ZA31

involved_in

GO:0002091: negative regulation of receptor internalization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0097060: synaptic membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0043197: dendritic spine

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

located_in

GO:0008021: synaptic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZA31

involved_in

GO:2000645: negative regulation of receptor catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:D3ZA31

involved_in

GO:2000643: positive regulation of early endosome to late endosome transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:D3ZA31

involved_in

GO:0045806: negative regulation of endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:D3ZA31

involved_in

GO:0097062: dendritic spine maintenance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:D3ZA31

involved_in

GO:0090394: negative regulation of excitatory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:LAMP1

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:LAMP1

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:DLG3

enables

GO:0019903: protein phosphatase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:D3ZA31

F

Seeded From UniProt

complete

RAT:DLG2

enables

GO:0019903: protein phosphatase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:D3ZA31

F

Seeded From UniProt

complete

RAT:DLG4

enables

GO:0019903: protein phosphatase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:D3ZA31

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.