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Rho-linked genes and neurological disorders

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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.

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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

Aβ:

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

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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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Authors and Affiliations

  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Demerec Building, Cold Spring Harbor, NY, 11724, USA

    Nael Nadif Kasri & Linda Van Aelst

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  1. Nael Nadif Kasri
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  2. Linda Van Aelst
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Correspondence to Linda Van Aelst.

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Nadif Kasri, N., Van Aelst, L. Rho-linked genes and neurological disorders. Pflugers Arch - Eur J Physiol 455, 787–797 (2008). https://doi.org/10.1007/s00424-007-0385-1

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  • DOI: https://doi.org/10.1007/s00424-007-0385-1

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