ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling.

Nature Communications
XiaoYun SunYuHua Sun

Abstract

ADNP (Activity Dependent Neuroprotective Protein) is a neuroprotective protein whose aberrant expression has been frequently linked to neural developmental disorders, including the Helsmoortel-Van der Aa syndrome (also called the ADNP syndrome). However, its role in neural development and pathology remains unclear. Here, we show that ADNP is required for neural induction and differentiation by enhancing Wnt signaling. Mechanistically, ADNP functions to stabilize β-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex: Axin and APC. Loss of ADNP promotes the formation of the degradation complex and β-Catenin degradation via ubiquitin-proteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. In addition, adnp gene disruption in zebrafish leads to defective neurogenesis and reduced Wnt signaling. Our work provides important insights into the role of ADNP in neural development and the pathology of the Helsmoortel-Van der Aa syndrome caused by ADNP gene mutation.

References

Oct 3, 2000·The Journal of Biological Chemistry·R ZamostianoI Gozes
Jul 31, 2003·Brain Research. Developmental Brain Research·Albert PinhasovIllana Gozes
May 5, 2004·The Journal of Biological Chemistry·Inna DivinskiIllana Gozes
Aug 28, 2007·The Journal of Pharmacology and Experimental Therapeutics·Inna Vulih-ShultzmanIllana Gozes
Sep 20, 2007·The Journal of Biological Chemistry·Shmuel Mandel, Illana Gozes
Sep 21, 2007·Journal of Cell Science·Wenqing Xu, David Kimelman
Oct 12, 2012·PLoS Biology·Shu-Yu WuLilianna Solnica-Krezel
Feb 6, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Ellen C Jensen
Feb 18, 2014·Nature Genetics·Céline HelsmoortelNathalie Van der Aa
Jun 8, 2014·Experimental Cell Research·Raul Bardini BressanAndrea Gonçalves Trentin
Aug 30, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Geert VandeweyerR Frank Kooy
Oct 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Aarathi SugathanMichael E Talkowski
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Zhuojin XuRandall T Moon
Aug 15, 2018·The Journal of Clinical Investigation·Gal Hacohen-KleimanIllana Gozes
Oct 17, 2018·Frontiers in Cell and Developmental Biology·Xiaoyun SunYuhua Sun
Nov 13, 2018·Current Pharmaceutical Design·Yanina Ivashko-Pachima, Illana Gozes

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
RNA-seq
transgenic
immunoprecipitation
co-immunoprecipitation
Co-IP
pull down
pull-downed
PCR
Co-IPs

Software Mentioned

IP
Mass Spec
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.