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Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 5, pp 787–797 | Cite as

Rho-linked genes and neurological disorders

  • Nael Nadif Kasri
  • Linda Van AelstEmail author
Invited Review

Abstract

Mental retardation (MR) is a common cause of intellectual disability and affects approximately 2 to 3% of children and young adults. Many forms of MR are associated with abnormalities in dendritic structure and/or dendritic spine morphology. Given that dendritic spine morphology has been tightly linked to synaptic activity, altered spine morphology has been suggested to underlie or contribute to the cognitive disabilities associated with MR. The structure and dynamics of dendritic spines is determined by its underlying actin cytoskeleton. Signaling molecules and cascades important for cytoskeletal regulation have therefore attracted a great deal of attention. As key regulators of both the actin and microtubule cytoskeletons, it is not surprising that the Rho GTPases have emerged as important regulators of dendrite and spine structural plasticity. Significantly, mutations in regulators and effectors of Rho GTPases have been associated with diseases affecting the nervous system, including MR and amyotropic lateral sclerosis (ALS). Here, we will discuss Rho GTPase-related genes and their signaling pathways involved in MR and ALS.

Keywords

Mental retardation Dendritic spines Actin cytoskeleton Rho GTPases X-linked mental retardation Amyotrophic lateral sclerosis 

Abbreviations

AD

Alzheimer disease

ALS

amyotropic lateral sclerosis

AMPAR

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

ARHGEF6

Rho guanine–nucleotide exchange factor 6

Arp2/3

actin-related proteins 2 and 3

amyloid β

CREB

cAMP-responsive element-binding protein

CYFIP

cytoplasmic FMR1 interacting protein

FMRP

fragile-X mental retardation protein

FMR1

fragile-X mental retardation-1 gene

FRAXA

fragile-X syndrome

GAP

GTPase activating proteins

GDI

guanine–nucleotide dissociation inhibitor

GEF

guanine–nucleotide exchange factor

LIM

Lin-11, Isl-1, and Mec-3 kinase

LTD

long-term depression

LTP

long-term potentiation

MEGAP

mental disorder-associated GAP protein

mGluR

metabotropic glutamate receptor

MLC

myosin light chain

MLCK

myosin light chain kinase

MLCP

myosin light chain phosphatase

MR

mental retardation

MRX

non-syndromic X-linked mental retardation

MRXS

syndromic X-linked mental retardation

OPHN1

oligophrenin-1

PAK

p21-activated kinases

ROCK

Rho-Kinase

WASP

Wiskott–Aldrich syndrome protein

WAVE

WASP family Verprolin-homologous protein

WS

Williams–Beuren syndrome

XLMR

X-linked mental retardation

Notes

Acknowledgements

L.V.A is supported by the National Institutes of Health, National Science Foundation, and National Alliance for Autism Research. N.N.K is a postdoctoral fellow from the Fund for Scientific Research Flanders and is supported by the Human Frontiers Science Program.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Cold Spring Harbor LaboratoryCold Spring HarborUSA

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