• Julie Tastet, Hélène Cuberos, Béatrice Vallée, Annick Toutain, Martine Raynaud, Sylviane Marouillat, Rose-Anne Thépault, Frédéric Laumonnier, Frédérique Bonnet-Brilhault, Patrick Vourc'h, Christian R Andres, and Hélène Bénédetti.
• UMR INSERM U1253, Université François Rabelais, Tours, France; CNRS UPR 4301, CBM, Orléans, France; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
• Neuroscience. 2019 Feb 10; 399: 199-210.

AbstractLIMK2 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.Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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