TY - JOUR
T1 - βiI-spectrin promotes mouse brain connectivity through stabilizing axonal plasma membranes and enabling axonal organelle transport
AU - Lorenzo, Damaris N.
AU - Badea, Alexandra
AU - Zhou, Ruobo
AU - Mohler, Peter J.
AU - Zhuang, Xiaowei
AU - Bennett, Vann
N1 - Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
PY - 2019/7/30
Y1 - 2019/7/30
N2 - βII-spectrin is the generally expressed member of the β-spectrin family of elongated polypeptides that form micrometer-scale networks associated with plasma membranes. We addressed in vivo functions of βII-spectrin in neurons by knockout of βII-spectrin in mouse neural progenitors. βII-spectrin deficiency caused severe defects in long-range axonal connectivity and axonal degeneration. βII-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 βII-spectrin associates with KIF3A, KIF5B, KIF1A, and dynactin, implicating spectrin in the coupling of motors and synaptic cargo. βII-spectrin required phosphoinositide lipid binding to promote axonal transport and restore axon growth. Knockout of ankyrin-B (AnkB), a βII-spectrin partner, primarily impaired retrograde organelle transport, while double knockout of βII-spectrin and AnkB nearly eliminated transport. Thus, βII-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.
AB - βII-spectrin is the generally expressed member of the β-spectrin family of elongated polypeptides that form micrometer-scale networks associated with plasma membranes. We addressed in vivo functions of βII-spectrin in neurons by knockout of βII-spectrin in mouse neural progenitors. βII-spectrin deficiency caused severe defects in long-range axonal connectivity and axonal degeneration. βII-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 βII-spectrin associates with KIF3A, KIF5B, KIF1A, and dynactin, implicating spectrin in the coupling of motors and synaptic cargo. βII-spectrin required phosphoinositide lipid binding to promote axonal transport and restore axon growth. Knockout of ankyrin-B (AnkB), a βII-spectrin partner, primarily impaired retrograde organelle transport, while double knockout of βII-spectrin and AnkB nearly eliminated transport. Thus, βII-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.
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U2 - 10.1073/pnas.1820649116
DO - 10.1073/pnas.1820649116
M3 - Article
C2 - 31209033
AN - SCOPUS:85070012154
SN - 0027-8424
VL - 116
SP - 15686
EP - 15695
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -