Small, smaller… dendritic spine

Abstract

Spines are highly motile protrusions emerging from the dendritic shafts of neurons. The dynamics of these postsynaptic structures are ruled by actin filament turnover. However, our understanding of the mechanisms of actin polymerization in dendritic spines is quite ambiguous. A recent study by the Giannone laboratory (Chazeau et al, 2014) is now shedding some light on the peculiar features of actin polymerization in dendritic spines, which are distinct from the known canonical mechanisms.See also: A Chazeau et al (December 2014) C ell biologists live with dogmas, and one of the best kept ones is that actin polymerization in a cell should always occur from the plasma membrane where the fast incorporation of actin monomers into newly formed short filaments generates the force and meshwork to push out and stabilize the membrane. Understanding the mechanisms that regulate this process is fundamental for life since virtually any kind of cell motility relies on directed actin polymerization. As odd as it may sound, even the way we feel, what we memorize and what we might forget is ultimately controlled by actin polymerization in the synapses of neurons.The complexity of actin polymerization in vivo is staggering as the collective work over more than 30 years has shown, and still controversial discussions are ongoing on the role of the participating protein complexes and actin-binding proteins, as well as the spatial organization of actin filaments. Without entering the disputable matter, it is generally accepted in the field that in areas of actin polymerization, such as the lamellipodia, nucleation promoting factors (NPFs) are activated at the plasma membrane (Lai et al, 2008), as well as actin nucleators such as the Arp2/3 complex, formins, or WH2 domain-containing nucleators (Campellone & Welch, 2010), which then promote de novo formation of actin filaments and incorporation of monomers into the growing filaments in order to exert protruding force (Rottner et al, 1999).So far, so good. What we tend to neglect though is that our current view on the spatial organization of actin polymerization in cells is biased by what cultured cells can actually perform on a two-dimensional stiff substrate. These conditions promote the formation of highly esthetic structures such as filopodia, lamellipodia, crowns-just to name some of the most studied. The beauty of this system is that it allows excellent imaging to dissect the spatiotemporal sequence of actin polymerization and to define the underlying structural filament meshwork. This has collectively added to our current picture of membrane-linked actin polymerization and the concept of retrograde F-actin flow from the cell membrane toward the cell center. This mechanism is unquestionably true for most membrane protrusions observed in cultured cells; however, it has remained unclear whether it also applies to actin dynamics in tissue-constrained cells and extremely small membrane compartments such as the dendritic spines.In neurons, the post-synaptic terminals of most excita...

Mechanical coupling between transsynaptic N-cadherin adhesions and actin flow stabilizes dendritic spines

“…, 2014 ) might be related to such trapping of actin filaments. Overall our model, which considers a very polarized flow within a homogeneous actin population, provides a good quantitative interpretation of most of the experiments performed here, but the actual situation might be more complex ( Pilo Boyl and Witke, 2014 ). Indeed, there is ongoing debate about the polarity of actin filaments within dendritic filopodia and spines.…”