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Regulating filopodial dynamics through actin-depolymerizing factor/cofilin.

Abstract

The regulation of filopodial dynamics by neurotrophins and other guidance cues plays an integral role in growth cone pathfinding. Filopodia are F-actin-based structures that explore the local environment, generate forces and play a role in growth cone translocation. Here, we review recent research showing that the actin-depolymerizing factor (ADF)/cofilin family of proteins mediates changes in the length and number of growth cone filopodia in response to brain-derived neurotrophic factor (BDNF). Although inhibition of myosin contractility also causes filopodial elongation, the elongation in response to BDNF does not occur through a myosin-dependent pathway. Active ADF/cofilin increases the rate of cycling between the monomer and polymer pools and is critical for the BDNF-induced changes. Thus, we discuss potential mechanisms by which ADF/cofilin may affect filopodial initiation and length change via its effects on F-actin dynamics in light of past research on actin and myosin function in growth cones.

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BibTeXRIS

Joseph Fass, Scott Gehler, Patrick Sarmiere, Paul Letourneau, James R Bamburg. 2004. Regulating filopodial dynamics through actin-depolymerizing factor/cofilin.. https://doi.org/10.1111/j.1447-073x.2004.00087.x

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Actin Depolymerizing Factors↗

Actin is not an essential component in the mechanism of calcium-triggered vesicle fusion.

Actin has been suggested as an essential component in the membrane fusion stage of exocytosis. In some model systems disruption of the actin filament network associated with exocytotic membranes results in a decrease in secretion. Here we analyze the fast Ca2+-triggered membrane fusion steps of regulated exocytosis using a stage-specific preparation of native secretory vesicles (SV) to directly test whether actin plays an essential role in this mechanism. Although present on secretory vesicles, selective pharmacological inhibition of actin did not affect the Ca2+-sensitivity, extent, or kinetics of membrane fusion, nor did the addition of exogenous actin or an anti-actin antibody. There was also no discernable affect on inter-vesicle contact (docking). Overall, the results do not support a direct role for actin in the fast, Ca2+-triggered steps of regulated membrane fusion. It would appear that actin acts elsewhere within the exocytotic cycle.

Actin Depolymerizing Factors↗

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