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Tastet J., Cuberos H., Vallée B., Toutain A., Raynaud M., Marouillat S., Thépault R.-A., Laumonnier F., Bonnet-Brilhault F., Vourc’h P., Andres C. R. and Bénédetti H.

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

Neuroscience, (2019) 399, 199-210.

par Frapart - publié le

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.