Title:	Development of the axonal βII-spectrin periodic skeleton requires active cytoskeletal remodelling
Authors:	Bodas, Shivani Mishra, Ashish Pullarkat, Pramod Ghose, Aurnab
Issue Date:	28-Jul-2025
Publisher:	eLife Sciences Publications Ltd
Citation:	elife, 2025, Vol. 1, Article No.107797
Abstract:	The axonal membrane-associated periodic skeleton (MPS), consisting of F-actin rings crosslinked by spectrin heterotetramers, is ubiquitous and critical for neuronal function and homoeostasis. However, the initiation and early development of the axonal MPS are poorly understood. Using superresolution imaging, we show that βII-spectrin is recruited early to the axonal cortex, followed by progressive establishment of long-range periodic order. Microtubule dynamics are essential for MPS formation in the early stages, but transition to a passive stabilising role in mature axons. We show that the early subplasmalemmal recruitment of βII-spectrin is dependent on cortical actin but not on actomyosin contractility, and active nucleation of F-actin is required in early development but is dispensable for the mature MPS. Using a βII-spectrin knockout model, we demonstrate that the actin-binding and lipid-interacting domains of βII-spectrin are critical for its subplasmalemmal confinement and, subsequently, MPS maturation. These findings highlight stage-specific cytoskeletal remodelling underlying MPS development and advance our understanding of axonal subcellular architecture.
Description:	Open Access.
URI:	http://hdl.handle.net/2289/8640
ISSN:	2050-084X
Alternative Location:	https://www.biorxiv.org/content/10.1101/2025.02.19.639207v2 https://doi.org/10.1101/2025.02.19.639207
Copyright:	eLife Sciences Publications Ltd
Additional information:	This study examines how the neuronal cytoskeleton contributes to the formation of the axonal membrane-associated periodic skeleton (MPS) in embryonic dorsal root ganglia (DRG) neurons, using STED imaging. Conclusions are supported by convincing methods, data, and analyses. This useful work confirms previous data and improves our understanding of the roles of microtubules and actin dynamics in the chronological recruitment of MPS components.
Appears in Collections:	Research Papers (SCM)

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