Abstract
Actin, spectrin, and associated molecules form a periodic sub-membrane lattice structure in axons. How this membrane skeleton is developed and why it preferentially forms in axons are unknown. Here, we studied the developmental mechanism of this lattice structure. We found that this structure emerged early during axon development and propagated from proximal regions to distal ends of axons. Components of the axon initial segment were recruited to the lattice late during development. Formation of the lattice was regulated by the local concentration of βII spectrin, which is higher in axons than in dendrites. Increasing the dendritic concentration of βII spectrin by overexpression or by knocking out ankyrin B induced the formation of the periodic structure in dendrites, demonstrating that the spectrin concentration is a key determinant in the preferential development of this structure in axons and that ankyrin B is critical for the polarized distribution of βII spectrin in neurites.
Highlights
Neurons are highly polarized cells with their somatodendritic regions receiving synaptic inputs and axons propagating electrical signals and sending synaptic outputs to target cells
In order to determine the developmental course of the periodic membrane skeletal structure, we fixed dissociated neurons at different developmental stages, immunostained for βII spectrin, and imaged using stochastic optical reconstruction microscopy (STORM), a super-resolution imaging method that relies on switching and localizing single molecules to acquire sub-diffraction limit images (Betzig et al, 2006; Hess et al, 2006; Rust et al, 2006; Huang et al, 2008)
Since a single actin filament can interact with multiple spectrin tetramers, and a single spectrin tetramer can bind to two actin filaments, one at each end of the symmetric tetramer (Bennett and Lorenzo, 2013), we reason that these crosslinking interactions are responsible for the formation of the lattice structure
Summary
Neurons are highly polarized cells with their somatodendritic regions receiving synaptic inputs and axons propagating electrical signals and sending synaptic outputs to target cells. Cytoskeletal proteins are important for maintaining the polarity of neurons. Increasing evidence suggests an important role for spectrin in the maintenance of neuronal polarization, as well as the development and stabilization of axons (Hammarlund et al, 2007; Galiano et al, 2012). ΑII and βII spectrin are enriched in axons (Riederer et al, 1986; Galiano et al, 2012). Spectrin is known to be important for providing the mechanical stability for axons (Hammarlund et al, 2007) and protecting them from mechanical stress (Krieg et al, 2014), for axon path finding (Hulsmeier et al, 2007), for the stabilization of pre-synaptic terminals (Pielage et al, 2005), and for maintaining specific membrane domains in axons (Susuki and Rasband, 2008). Spectrin has been shown to play a role in human neurological diseases (Ikeda et al, 2006; Writzl et al, 2012)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
