Imbalance of synaptic actin dynamics as a key to the Fragile X syndrome?

Abstract

Our experiences and memories define who we are and evidence accumulates that memory formation is dependent on functional and structural adaptations of synaptic structures in our brain. Especially dendritic spines, the postsynaptic compartments of synapses, show a strong structure-to-function relationship and a high degree of structural plasticity. Although the molecular mechanisms are not completely understood, it is known that these modifications are highly dependent on the actin-cytoskeleton, the major cytoskeletal component of the spine. Given the crucial involvement of actin in these mechanisms, dysregulations of spine actin dynamics (reflected by alterations in dendritic spine morphology) can be found in a variety of neurological disorders ranging from schizophrenia to several forms of autism spectrum disorders like the Fragile X Syndrome (FXS). FXS is caused by a single mutation leading to an inactivation of the X-linked fragile X mental retardation 1 gene and loss of its gene product, the RNA-binding protein Fragile X Mental Retardation Protein 1 (FMRP) which normally can be found both pre- and postsynaptically. FMRP is involved in mRNA transport as well as regulation of local translation at the synapse and although hundreds of FMRP-target mRNAs could be identified only very few interactions between FMRP and actin-regulating proteins were reported and validated. In this review we want to give an overview about recent work by our lab and others providing evidence that dysregulated actin dynamics might indeed be at the very base of a deeper understanding of neurological disorders ranging from cognitive impairment to the autism spectrum.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2GtvPf0
via IFTTT