Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May;15(5):713-21.
doi: 10.1038/nn.3080.

An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin

Valentina Lo Sardo  1 , Chiara Zuccato, Germano Gaudenzi, Barbara Vitali, Catarina Ramos, Marzia Tartari, Michael A Myre, James A Walker, Anna Pistocchi, Luciano Conti, Marta Valenza, Binia Drung, Boris Schmidt, James Gusella, Scott Zeitlin, Franco Cotelli, Elena Cattaneo
Affiliations

An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin

Valentina Lo Sardo et al. Nat Neurosci. 2012 May.

Abstract

The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Neurochem. 2003 Oct;87(1):101-6 - PubMed
    1. Dis Model Mech. 2009 May-Jun;2(5-6):247-66 - PubMed
    1. Nat Neurosci. 2007 Jul;10(7):838-45 - PubMed
    1. Trends Genet. 1994 Mar;10(3):73-4 - PubMed
    1. Genes Dev. 2006 Dec 1;20(23):3199-214 - PubMed

Publication types

MeSH terms

Substances