Networks of Polarized Actin Filaments in the Axon Initial Segment Provide a Mechanism for Sorting Axonal and Dendritic Proteins

SummaryTrafficking of proteins specifically to the axonal or somatodendritic membrane allows neurons to establish and maintain polarized compartments with distinct morphology and function. Diverse evidence suggests that an actin-dependent vesicle filter within the axon initial segment (AIS) plays a critical role in polarized trafficking; however, no distinctive actin-based structures capable of comprising such a filter have been found within the AIS. Here, using correlative light and scanning electron microscopy, we visualized networks of actin filaments several microns wide within the AIS of cortical neurons in culture. Individual filaments within these patches are predominantly oriented with their plus ends facing toward the cell body, consistent with models of filter selectivity. Vesicles carrying dendritic proteins are much more likely to stop in regions occupied by the actin patches than in other regions, indicating that the patches likely prevent movement of dendritic proteins to the axon and thereby act as a vesicle filter.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 2 μm diameter actin networks are visualized by SEM and light microscopy in the AIS ► Actin filaments within networks are oriented with their plus ends facing proximally ► Actin network structure suggests a mechanism for selectively halting vesicles ► Vesicles carrying dendritic proteins halt and reverse in actin networks