LIMK2-1 is a Hominidae-Specific Isoform of LIMK2 Expressed in Central Nervous System and Associated with Intellectual Disability. (10th February 2019)

• Record Type: Journal Article
• Authors: Tastet, Julie; Cuberos, Hélène; Vallée, Béatrice; Toutain, Annick; Raynaud, Martine; Marouillat, Sylviane; Thépault, Rose-Anne; Laumonnier, Frédéric; Bonnet-Brilhault, Frédérique; Vourc'h, Patrick; Andres, Christian R.; Bénédetti, Hélène
• Is Part Of: Neuroscience. Volume 399(2019)
• Page Start: 199
• Page End: 210
• Publication Date: 2019-02-10
• Subjects: PP1i phosphatase 1 inhibitory domain -- ID intellectual disability -- LIMK LIM kinase; LIM kinase -- hominidae-specific -- neuron morphology -- cytoskeleton remodeling -- intellectual deficiency -- patient mutation; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.12.017
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: LIMK2-1 is a new LIMK2 isoform which is hominidae-specific. LIMK2-1 is expressed at the protein level in human fetal brain and faintly in adult brain. The rare missense variant S668P in LIMK2-1 PP1i domain is associated to intellectual disability. LIMK2-1 plays a role in neurite outgrowth and neurons arborization. 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.