LIMK2-1 is a Hominidae-Specific Isoform of LIMK2 Expressed in Central Nervous System and Associated with Intellectual Disability

Abstract : LIMK2 is involved in neuronal functions by regulating actin dynamics. Different isoforms of LIMK2 are described in databanks. LIMK2a and LIMK2b are the most characterized. A few pieces of evidence suggest that LIMK2 isoforms might not have overlapping functions. In this study, we focused our attention on a less studied human LIMK2 isoform, LIMK2-1. Compared to the other LIMK2 isoforms, LIMK2-1 contains a supplementary C-terminal phosphatase 1 inhibitory domain (PP1i). We found out that this isoform was hominidae-specific and showed that it was expressed in human fetal brain and faintly in adult brain. Its coding sequence was sequenced in 173 patients with sporadic non-syndromic intellectual disability (ID), and we observed an association of a rare missense variant in the PP1i domain (rs151191437, p.S668P) with ID. Our results also suggest an implication of LIMK2-1 in neurite outgrowth and neurons arborization which appears to be affected by the p.S668P variation. Therefore our results suggest that LIMK2-1 plays a role in the developing brain, and that a rare variation of this isoform is a susceptibility factor in ID.
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Submitted on : Thursday, March 14, 2019 - 11:41:22 AM
Last modification on : Thursday, July 11, 2019 - 4:04:02 PM

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Julie Tastet, Hélène Cuberos, Béatrice Vallée, Annick Toutain, Martine Raynaud, et al.. LIMK2-1 is a Hominidae-Specific Isoform of LIMK2 Expressed in Central Nervous System and Associated with Intellectual Disability. Neuroscience, Elsevier - International Brain Research Organization, 2019, 399, pp.199-210. ⟨10.1016/j.neuroscience.2018.12.017⟩. ⟨hal-02067472⟩

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