The XLID protein PQBP1 and the GTPase Dynamin 2 define a signaling link that orchestrates ciliary morphogenesis in postmitotic neurons

Yoshiho Ikeuchi, Luis delaTorre-Ubieta, Takahiko Matsuda, Hanno Steen, Hitoshi Okazawa, Azad Bonni

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Intellectual disability (ID) is a prevalent developmental disorder of cognition that remains incurable. Here, we report that knockdown of the X-linked ID(XLID) protein polyglutamine-binding protein 1 (PQBP1) in neurons profoundly impairs the morphogenesis of the primary cilium, including in the mouse cerebral cortex invivo. PQBP1 is localized at the base of the neuronal cilium, and targeting its WW effector domain to the cilium stimulates ciliary morphogenesis. We also find that PQBP1 interacts with Dynamin 2 and thereby inhibits its GTPase activity. Accordingly, Dynamin 2 knockdown in neurons stimulates ciliogenesis and suppresses the PQBP1 knockdown-induced ciliary phenotype. Strikingly, a mutation of the PQBP1 WW domain that causes XLID disrupts its ability to interact with and inhibit Dynamin 2 and to induce neuronal ciliogenesis. These findings define PQBP1 and Dynamin 2 as components of a signaling pathway that orchestrates neuronal ciliary morphogenesis in the brain

Original languageEnglish
Pages (from-to)879-889
Number of pages11
JournalCell Reports
Volume4
Issue number5
DOIs
StatePublished - May 12 2013

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