Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What's behind Neuro-RACopathies

被引：22

作者：

Scala, Marcello ^{[1
,2
]}

Nishikawa, Masashi ^{[3
]}

Nagata, Koh-ichi ^{[3
,4
]}

Striano, Pasquale ^{[1
,2
]}

机构：

[1] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, I-16132 Genoa, Italy

[2] IRCCS Ist Giannina Gaslini, Pediat Neurol & Muscular Dis Unit, I-16147 Genoa, Italy

[3] Inst Dev Res, Aichi Dev Disabil Ctr, Dept Mol Neurobiol, 713-8 Kamiya, Kasugai, Aichi 4800392, Japan

[4] Nagoya Univ Grad Sch Med, Dept Neurochem, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan

来源：

CELLS | 2021年 / 10卷 / 12期

关键词：

Rho family guanosine triphosphatases; RAC1; RAC3; cytoskeletal dynamics; neuronal development; neurodevelopmental disorder; neuro-RACopathies; TRIO; DOCK; PAK; RHO-FAMILY GTPASE; MENTAL-RETARDATION; NMDA RECEPTOR; INTELLECTUAL DISABILITY; DIFFERENTIAL EXPRESSION; DEVELOPMENTAL DISORDERS; BINDING PROTEINS; EXCHANGE FACTORS; ARP2/3; COMPLEX; CELL-MIGRATION;

D O I：

10.3390/cells10123395

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Rho family guanosine triphosphatases (GTPases) regulate cellular signaling and cytoskeletal dynamics, playing a pivotal role in cell adhesion, migration, and cell cycle progression. The Rac subfamily of Rho GTPases consists of three highly homologous proteins, Rac 1-3. The proper function of Rac1 and Rac3, and their correct interaction with guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs) are crucial for neural development. Pathogenic variants affecting these delicate biological processes are implicated in different medical conditions in humans, primarily neurodevelopmental disorders (NDDs). In addition to a direct deleterious effect produced by genetic variants in the RAC genes, a dysregulated GTPase activity resulting from an abnormal function of GEFs and GAPs has been involved in the pathogenesis of distinctive emerging conditions. In this study, we reviewed the current pertinent literature on Rac-related disorders with a primary neurological involvement, providing an overview of the current knowledge on the pathophysiological mechanisms involved in the neuro-RACopathies.

引用

页数：23