The Capping Activity of Eps8 Regulates Axonal F-Actin Patch Dynamics and the Formation of Collateral Branch

Abstract

Axon collateral branching is a critical process that enables neurons to form complex neural circuits and exhibit neural plasticity. Collateral branching is a highly cytoskeletal-dependent process that is initiated by the formation of dynamic F-actin patches. However, the regulatory mechanisms governing these actin patches' dynamics are poorly understood. Eps8, a capping protein implicated in several neurodevelopmental disorders. We find that Eps8 plays a role in regulating actin patches and the formation of protrusions in chick spinal neurons. This study reveals that Eps8 colocalizes with actin patches. The capping activity of Eps8 regulates the lifetime and stability of actin patches but not initiation. We further investigated the counterbalancing activities of Eps8 and Fmn2 in regulating actin patches and protrusions. Spatiotemporal regulation of Eps8 and Fmn2 during protrusion formation was also studied using live imaging. Neurodevelopmental defects due to Eps8 may be associated with improper regulation of axon branching.