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. 2015 Sep 3;13(9):e1002241.
doi: 10.1371/journal.pbio.1002241. eCollection 2015.

Short Lives with Long-Lasting Effects: Filopodia Protrusions in Neuronal Branching Morphogenesis

George Leondaritis  1 , Britta Johanna Eickholt  2
Affiliations

Short Lives with Long-Lasting Effects: Filopodia Protrusions in Neuronal Branching Morphogenesis

George Leondaritis et al. PLoS Biol. .

Abstract

The branching behaviors of both dendrites and axons are part of a neuronal maturation process initiated by the generation of small and transient membrane protrusions. These are highly dynamic, actin-enriched structures, collectively called filopodia, which can mature in neurons to form stable branches. Consequently, the generation of filopodia protrusions is crucial during the formation of neuronal circuits and involves the precise control of an interplay between the plasma membrane and actin dynamics. In this issue of PLOS Biology, Hou and colleagues identify a Ca2+/CaM-dependent molecular machinery in dendrites that ensures proper targeting of branch formation by activation of the actin nucleator Cobl.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Filopodia formation in five steps.
1. Under resting conditions, actin nucleators (blue and green crosses), filament bundling and crosslinking proteins (grey crosses), and membrane curvature–sensing proteins (purple and orange curved lines) reside in the cytosol and preserve a base-line level of filamentous (F-) actin (red lines). Black dots denote plasma membrane microdomains rich in specific lipids and transmembrane proteins. 2. Upon signaling (e.g., increases in Ca2+ in the cytosol or activation of growth factor induced Phosphatidylinositol-4,5-bisphosphate (PIP2)-Phosphatidylinositol-3,4,5-trisphosphate (PIP3) turnover), nucleators are activated and, together with elongation factors, promote rapid actin polymerization and actin patch formation. 3. Filaments extend rapidly towards the membrane, and changes in membrane curvature are sensed and/or induced by curvature-sensing proteins. 4. A growing filopodium has established a mixture of unbundled and bundled or crosslinked actin filaments. It is conceivable that different sets of nucleators and elongators may contribute to increased actin polymerization. Other proteins that uncap or cap barbed ends or proteins that sever filaments at the root of filopodia may regulate filament turnover during this process. 5. In a “mature” filopodium, additional signals may guide microtubule invasion in order to stabilize the nascent filopodium into a branch.
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