Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory

Molecular Psychiatry
N AmramIllana Gozes

Abstract

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences. RNA sequencing evaluations showed major age, sex and genotype differences. Function enrichment and focus on major gene expression changes further implicated channel/transporter function and the cytoskeleton. In particular, a significant maturation change (1 month-five months) was observed in beta1 tubulin (Tubb1) mRNA, only in Adnp(+/+) males, and sex-dependent increase in calcium channel mRNA (Cacna1e) in Adnp(+/+) males compared with females. At the protein level, the Adnp(+/-) mice exhibited impaired hippocampal expression of the calcium channel (voltage-dependent calcium channel, Cacnb1) as well as other key ASD-li...Continue Reading

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Citations

Jan 28, 2016·Journal of Molecular Neuroscience : MN·Yanina Ivashko PachimaIllana Gozes
Jan 28, 2016·Journal of Molecular Neuroscience : MN·Illana GozesAnat Idan-Feldman
Feb 22, 2017·Translational Psychiatry·I GozesS Bedrosian-Sermone
Dec 3, 2016·Scientific Reports·Shmma QuraisheAmritpal Mudher
Mar 6, 2018·Current Psychiatry Reports·Sarah L FerriEdward S Brodkin
Sep 25, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Shlomo SragovichIllana Gozes
Aug 15, 2018·The Journal of Clinical Investigation·Gal Hacohen-KleimanIllana Gozes
Jan 22, 2019·Translational Psychiatry·Shlomo SragovichIllana Gozes
Dec 25, 2019·Journal of Neuroscience Research·Adele Mossa, M Chiara Manzini
Sep 20, 2019·Translational Psychiatry·Shlomo SragovichIllana Gozes
Jun 27, 2020·Journal of Molecular Neuroscience : MN·Yanina Ivashko-Pachima, Illana Gozes
Jul 17, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yarden ZivSegev Barak
Dec 12, 2018·Frontiers in Neuroscience·Illana Gozes
Aug 24, 2018·Frontiers in Cellular Neuroscience·Artemis VaridakiEleanor T Coffey
Oct 22, 2019·Frontiers in Cellular Neuroscience·Yanina Ivashko-Pachima, Illana Gozes
May 28, 2019·Journal of Molecular Neuroscience : MN·Joseph LevineIllana Gozes
Jul 15, 2020·Translational Psychiatry·Iris GriggIllana Gozes
Jan 4, 2019·Journal of Molecular Neuroscience : MN·Joanna A RuszkiewiczMichael Aschner
Dec 18, 2020·Frontiers in Neurology·Illana Gozes
Aug 8, 2020·American Journal of Human Genetics·Michael S BreenSilvia De Rubeis
May 13, 2021·EMBO Reports·Francesco Longo, Eric Klann
Dec 19, 2021·Cell & Bioscience·Zhiqiang DengZhenyu Yue

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