Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A Cdh1-APC/FMRP Ubiquitin Signaling Link Drives mGluR-Dependent Synaptic Plasticity in the Mammalian Brain.

Neuron | 2015

Deregulation of synaptic plasticity may contribute to the pathogenesis of developmental cognitive disorders. In particular, exaggerated mGluR-dependent LTD is featured in fragile X syndrome, but the mechanisms that regulate mGluR-LTD remain incompletely understood. We report that conditional knockout of Cdh1, the key regulatory subunit of the ubiquitin ligase Cdh1-anaphase-promoting complex (Cdh1-APC), profoundly impairs mGluR-LTD in the hippocampus. Mechanistically, we find that Cdh1-APC operates in the cytoplasm to drive mGluR-LTD. We also identify the fragile X syndrome protein FMRP as a substrate of Cdh1-APC. Endogenous Cdh1-APC forms a complex with endogenous FMRP, and knockout of Cdh1 impairs mGluR-induced ubiquitination and degradation of FMRP in the hippocampus. Knockout of FMRP suppresses, and expression of an FMRP mutant protein that fails to interact with Cdh1 phenocopies, the Cdh1 knockout phenotype of impaired mGluR-LTD. These findings define Cdh1-APC and FMRP as components of a novel ubiquitin signaling pathway that regulates mGluR-LTD in the brain.

Pubmed ID: 25913861 RIS Download

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

View all literature mentions

Cdc27 (AF3.1) (antibody)

RRID:AB_627228

This monoclonal targets Human CDC27

View all literature mentions

HA-influenza (antibody)

RRID:AB_257974

This monoclonal targets HA

View all literature mentions

ANTI-FLAG(R) M2 Affinity Gel (antibody)

RRID:AB_10063035

This unknown targets ANTI-FLAG(R) M2 Affinity Gel

View all literature mentions

FMRP antibody (antibody)

RRID:AB_2278530

This polyclonal targets FMR1

View all literature mentions

MetaMorph Microscopy Automation and Image Analysis Software (software resource)

RRID:SCR_002368

Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.

View all literature mentions

pClamp (software resource)

RRID:SCR_011323

Software suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.

View all literature mentions

IGOR Pro (software resource)

RRID:SCR_000325

Software used for visualizing and graphing data, image processing, and programming. It is designed for use by scientists and engineers and supports large data sets, evenly spaced data, and various data import formats. The software includes a suite of image processing operations for image filtering, manipulation, and quantification and is completely programmable.

View all literature mentions