Asset Details

MbrlCatalogueTitleDetail

Do you wish to reserve the book?

Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling

by Hanganu-Opatz, Ileana L , Richter, Melanie , Schwanke, Birgit , Lerch, Jason P , Murtaza, Nadeem , Kwan, Vickie , Ellegood, Jacob , Walker, Susan , Morellini, Fabio , Kraus, Vanessa , Fiehler, Jens , Schweizer, Michaela , Scharrenberg, Robin , Yuen, Ryan K C , Sedlacik, Jan , White, Sean H , Scherer, Stephen W , Dörk, Ronja , Singh, Karun K , Hartung, Henrike , Johanns, Ole , Bedürftig, Bianca , Froylan Calderon de Anda , Scharf, Sarah , Lindenmaier, Zsuzsa , Henis, Melad , Hellmann, Jakob

in Anxiety / Autism / Chromosome 16 / Cognitive ability / Cortex / Dendritic spines / Gene dosage / Genomes / Kinases / Mutation / Neural networks / Neurodevelopmental disorders / Neurotransmission / Phenotypes / RhoA protein / Social interactions / Synapses / Synaptogenesis

2019

Yes Please

Hey, we have placed the reservation for you!

By the way, why not check out events that you can attend while you pick your title.

Oops! Something went wrong.

Looks like we were not able to place the reservation. Kindly try again later.

Are you sure you want to remove the book from the shelf?

Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling

2019

Confirm

Do you wish to request the book?

Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling

2019

Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy

How would you like to get it?

Submit

We have requested the book for you!

Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.

Oops! Something went wrong.

Looks like we were not able to place your request. Kindly try again later.

Journal Article

Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling

Hanganu-Opatz, Ileana L,

Richter, Melanie,

Schwanke, Birgit,

Lerch, Jason P,

Murtaza, Nadeem,

Kwan, Vickie,

Ellegood, Jacob,

Walker, Susan,

Morellini, Fabio,

Kraus, Vanessa,

Fiehler, Jens,

Schweizer, Michaela,

Scharrenberg, Robin,

Yuen, Ryan K C,

Sedlacik, Jan,

White, Sean H,

Scherer, Stephen W,

Dörk, Ronja,

Singh, Karun K,

Hartung, Henrike,

Johanns, Ole,

Bedürftig, Bianca,

Froylan Calderon de Anda,

Scharf, Sarah,

Lindenmaier, Zsuzsa,

Henis, Melad,

Hellmann, Jakob

2019

Overview

Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of ASD families identified three de novo mutations in TAOK2 and functional analysis in mice and human cells revealed that all the mutations impair protein stability, but they differentially impact kinase activity, dendrite growth, and spine/synapse development. Mechanistically, loss of Taok2 activity causes a reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator of TAOK2-dependent synaptic development.

Share this book

Add to My Shelf

Publisher

Nature Publishing Group

Subject

/ Autism

/ Cortex