%0 Journal Article
%1 Lorenzo2019
%A Lorenzo, Damaris N.
%A Badea, Alexandra
%A Zhou, Ruobo
%A Mohler, Peter J.
%A Zhuang, Xiaowei
%A Bennett, Vann
%D 2019
%I National Academy of Sciences
%J Proceedings of the National Academy of Sciences of the United States of America
%K axon b2sp cytoskeleton growth microscopy neuro storm transport
%N 31
%P 15686--15695
%R 10.1073/pnas.1820649116
%T $\beta$iI-spectrin promotes mouse brain connectivity through stabilizing axonal plasma membranes and enabling axonal organelle transport
%V 116
%X $\beta$II-spectrin is the generally expressed member of the $\beta$-spectrin family of elongated polypeptides that form micrometer-scale networks associated with plasma membranes. We addressed in vivo functions of $\beta$II-spectrin in neurons by knockout of $\beta$II-spectrin in mouse neural progenitors. $\beta$II-spectrin deficiency caused severe defects in long-range axonal connectivity and axonal degeneration. $\beta$II-spectrin- null neurons exhibited reduced axon growth, loss of actin-spectrinbased periodic membrane skeleton, and impaired bidirectional axonal transport of synaptic cargo. We found that $\beta$II-spectrin associates with KIF3A, KIF5B, KIF1A, and dynactin, implicating spectrin in the coupling of motors and synaptic cargo. $\beta$II-spectrin required phosphoinositide lipid binding to promote axonal transport and restore axon growth. Knockout of ankyrin-B (AnkB), a $\beta$II-spectrin partner, primarily impaired retrograde organelle transport, while double knockout of $\beta$II-spectrin and AnkB nearly eliminated transport. Thus, $\beta$II-spectrin promotes both axon growth and axon stability through establishing the actin- spectrin-based membrane-associated periodic skeleton as well as enabling axonal transport of synaptic cargo.