Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A

Variants in the high confident autism spectrum disorder (ASD) gene ANK2 target both ubiquitously expressed 220 kDa ankyrin-B and neurospecific 440 kDa ankyrin-B (AnkB440) isoforms. Previous work showed that knock-in mice expressing an ASD-linked Ank2 variant yielding a truncated AnkB440 product exhi...

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Autores principales:	Blake A Creighton, Simone Afriyie, Deepa Ajit, Cristine R Casingal, Kayleigh M Voos, Joan Reger, April M Burch, Eric Dyne, Julia Bay, Jeffrey K Huang, ES Anton, Meng-Meng Fu, Damaris N Lorenzo
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	ankyrin autism growth cone ANK2 axon branching Sema 3a Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/617903977b8c47b6bcec06f59021d6f8
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spelling	oai:doaj.org-article:617903977b8c47b6bcec06f59021d6f82021-11-24T12:30:16ZGiant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A10.7554/eLife.698152050-084Xe69815https://doaj.org/article/617903977b8c47b6bcec06f59021d6f82021-11-01T00:00:00Zhttps://elifesciences.org/articles/69815https://doaj.org/toc/2050-084XVariants in the high confident autism spectrum disorder (ASD) gene ANK2 target both ubiquitously expressed 220 kDa ankyrin-B and neurospecific 440 kDa ankyrin-B (AnkB440) isoforms. Previous work showed that knock-in mice expressing an ASD-linked Ank2 variant yielding a truncated AnkB440 product exhibit ectopic brain connectivity and behavioral abnormalities. Expression of this variant or loss of AnkB440 caused axonal hyperbranching in vitro, which implicated AnkB440 microtubule bundling activity in suppressing collateral branch formation. Leveraging multiple mouse models, cellular assays, and live microscopy, we show that AnkB440 also modulates axon collateral branching stochastically by reducing the number of F-actin-rich branch initiation points. Additionally, we show that AnkB440 enables growth cone (GC) collapse in response to chemorepellent factor semaphorin 3 A (Sema 3 A) by stabilizing its receptor complex L1 cell adhesion molecule/neuropilin-1. ASD-linked ANK2 variants failed to rescue Sema 3A-induced GC collapse. We propose that impaired response to repellent cues due to AnkB440 deficits leads to axonal targeting and branch pruning defects and may contribute to the pathogenicity of ANK2 variants.Blake A CreightonSimone AfriyieDeepa AjitCristine R CasingalKayleigh M VoosJoan RegerApril M BurchEric DyneJulia BayJeffrey K HuangES AntonMeng-Meng FuDamaris N LorenzoeLife Sciences Publications Ltdarticleankyrinautismgrowth coneANK2axon branchingSema 3aMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ankyrin autism growth cone ANK2 axon branching Sema 3a Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	ankyrin autism growth cone ANK2 axon branching Sema 3a Medicine R Science Q Biology (General) QH301-705.5 Blake A Creighton Simone Afriyie Deepa Ajit Cristine R Casingal Kayleigh M Voos Joan Reger April M Burch Eric Dyne Julia Bay Jeffrey K Huang ES Anton Meng-Meng Fu Damaris N Lorenzo Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A
description	Variants in the high confident autism spectrum disorder (ASD) gene ANK2 target both ubiquitously expressed 220 kDa ankyrin-B and neurospecific 440 kDa ankyrin-B (AnkB440) isoforms. Previous work showed that knock-in mice expressing an ASD-linked Ank2 variant yielding a truncated AnkB440 product exhibit ectopic brain connectivity and behavioral abnormalities. Expression of this variant or loss of AnkB440 caused axonal hyperbranching in vitro, which implicated AnkB440 microtubule bundling activity in suppressing collateral branch formation. Leveraging multiple mouse models, cellular assays, and live microscopy, we show that AnkB440 also modulates axon collateral branching stochastically by reducing the number of F-actin-rich branch initiation points. Additionally, we show that AnkB440 enables growth cone (GC) collapse in response to chemorepellent factor semaphorin 3 A (Sema 3 A) by stabilizing its receptor complex L1 cell adhesion molecule/neuropilin-1. ASD-linked ANK2 variants failed to rescue Sema 3A-induced GC collapse. We propose that impaired response to repellent cues due to AnkB440 deficits leads to axonal targeting and branch pruning defects and may contribute to the pathogenicity of ANK2 variants.
format	article
author	Blake A Creighton Simone Afriyie Deepa Ajit Cristine R Casingal Kayleigh M Voos Joan Reger April M Burch Eric Dyne Julia Bay Jeffrey K Huang ES Anton Meng-Meng Fu Damaris N Lorenzo
author_facet	Blake A Creighton Simone Afriyie Deepa Ajit Cristine R Casingal Kayleigh M Voos Joan Reger April M Burch Eric Dyne Julia Bay Jeffrey K Huang ES Anton Meng-Meng Fu Damaris N Lorenzo
author_sort	Blake A Creighton
title	Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A
title_short	Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A
title_full	Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A
title_fullStr	Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A
title_full_unstemmed	Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A
title_sort	giant ankyrin-b mediates transduction of axon guidance and collateral branch pruning factor sema 3a
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/617903977b8c47b6bcec06f59021d6f8
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Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A

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