The structure and function of actin cytoskeleton in mature glutamatergic dendritic spines

Abstract

Dendritic spines are actin-rich protrusions from the dendritic shaft, considered to be the locus where most synapses occur, as they receive the vast majority of excitatory connections in the central nervous system (CNS). Interestingly, hippocampal spines are plastic structures that contain a dense array of molecules involved in postsynaptic signaling and synaptic plasticity. Since changes in spine shape and size are correlated with the strength of excitatory synapses, spine morphology directly reflects spine function. Therefore several neuropathologies are associated with defects in proteins located at the spines. The present work is focused on the spine actin cytoskeleton attending to its structure and function mainly in glutamatergic neurons. It addresses the study of the structural plasticity of dendritic spines associated with long-term potentiation (LTP) and the mechanisms that underlie learning and memory formation. We have integrated the current knowledge on synaptic proteins to relate this plethora of molecules with actin and actin-binding proteins. We further included recent findings that outline key uncharacterized proteins that would be useful to unveil the real ultrastructure and function of dendritic spines. Furthermore, this review is directed to understand how such spine diversity and interplay contributes to the regulation of spine morphogenesis and dynamics. It highlights their physiological relevance in the brain function, as well as it provides insights for pathological processes affecting dramatically dendritic spines, such as Alzheimer's disease.

Extracellular matrix protein reelin regulate dendritic spine density through CaMKIIβ

“…This is because dendritic spines have high concentrations of actin fibers at excitatory synapses, and actin affects the size and the synaptic strength of the dendritic spine [22][23]. Interestingly, recent studies have shown that Reelin alters the actin cytoskeleton dynamics through n-cofilin, which is important for dendiritc spine stability [24][25].…”

High-throughput sequencing of the synaptome in major depressive disorder

“…52 More broadly, abnormalities of size, density and shape of dendritic spines have been hypothesized to have a role in various brain disorders, including intellectual disability, 53 autism, 54 Alzheimer’s disease, 55 SCZ and BP, 56 as well as MDD. 57 There is also increasing evidence to suggest that they may additionally be involved in the regulation of mood: lowered spine densities have been found in postmortem brains with two prototypical mood disorders (BP and MDD) 56,57 ; in addition, chronic stress, long considered one of the most robust risk factors for mood disorders, has been associated with excessive pruning of dendritic spines; 58 and finally, the antidepressant ‘effect’ of both traditional and novel pharmacological agents has been proposed to be mediated by increased formation of dendritic spines in the prefrontal cortex.…”

Peptide regulation of cofilin activity in the CNS: A novel therapeutic approach for treatment of multiple neurological disorders

“…Gaining specificity by limiting the drug’s action to the cell type affected by AD is one approach to limiting the side effects of a new potential AD treatment. There are many neuron-specific signaling pathways that regulate cofilin phosphorylation levels, most of them mediated by proteins found localized at or near postsynaptic densities (Bellot et al, 2014; Spence and Soderling, 2015). Some of these pathways may be restricted to subsets of neurons in specific brain regions, such as the Pak3-mediated pathway involved in X-linked mental retardation (Allen et al, 1998).…”