2013
DOI: 10.1038/ncomms3532
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Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation

Abstract: Neurite growth requires two guanine nucleotide-binding protein polymers of tubulins and septins. However, whether and how those cytoskeletal systems are coordinated was unknown. Here we show that the acute knockdown or knockout of the pivotal septin subunit SEPT7 from cerebrocortical neurons impairs their interhemispheric and cerebrospinal axon projections and dendritogenesis in perinatal mice, when the microtubules are severely hyperacetylated. The resulting hyperstabilization and growth retardation of microt… Show more

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Cited by 116 publications
(105 citation statements)
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“…Here, we confirm that the number of spines of hippocampal neurons is not affected by the expression of HDAC4 3SA. HDAC6, HDAC5, and HDAC9 activity are thought to be involved in dendritogenesis specifically during the early stages of neurodevelopment (43)(44)(45). Our experiments uncovered that HDAC4 influences the structure of an established, complex dendritic tree at a developmental stage when most of dendritogenesis has taken place and the neurons are mature and have formed functional synaptically connected networks.…”
Section: Discussionmentioning
confidence: 79%
“…Here, we confirm that the number of spines of hippocampal neurons is not affected by the expression of HDAC4 3SA. HDAC6, HDAC5, and HDAC9 activity are thought to be involved in dendritogenesis specifically during the early stages of neurodevelopment (43)(44)(45). Our experiments uncovered that HDAC4 influences the structure of an established, complex dendritic tree at a developmental stage when most of dendritogenesis has taken place and the neurons are mature and have formed functional synaptically connected networks.…”
Section: Discussionmentioning
confidence: 79%
“…HDAC6 has been shown also to protect dopaminergic neurons from alpha-synuclein-induced toxicity 53 . For what concerns axonal pathology, MT stability must be regulated at an optimal level to allow axon and dendrites development in neuritogenesis, and it has been demonstrated that HDAC6 is required to provide efficient MT deacetylation 54 . Consistently, it has been shown that silencing of HDAC6 reduced neurite outgrowth and that its retransfection was able to revert to the normal phenotype 55 .…”
Section: Discussionmentioning
confidence: 99%
“…Septindeficiency-mediated microtubule stabilization and hyperacetylation have also been shown to contribute to the defects in neuronal morphogenesis observed in Sept7 −/− mice (Ageta-Ishihara et al, 2013). Interestingly, septins are involved in the direct recruitment of histone deacetylase 6 (HDAC6) to microtubules for de-acetylation of the tubulin subunits (Ageta-Ishihara et al, 2013). However, as MAP4 and HDAC6 are ubiquitously expressed, it is less likely that they act as the differential determinants for the septin dependence of cytokinesis.…”
Section: Does Microtubule Stability Determine Septin-dependence Of Mamentioning
confidence: 99%