| First Author | Lorenzo DN | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 31 | Pages | 15686-15695 |
| PubMed ID | 31209033 | Mgi Jnum | J:278339 |
| Mgi Id | MGI:6342694 | Doi | 10.1073/pnas.1820649116 |
| Citation | Lorenzo DN, et al. (2019) betaII-spectrin promotes mouse brain connectivity through stabilizing axonal plasma membranes and enabling axonal organelle transport. Proc Natl Acad Sci U S A 116(31):15686-15695 |
| abstractText | betaII-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 betaII-spectrin in neurons by knockout of betaII-spectrin in mouse neural progenitors. betaII-spectrin deficiency caused severe defects in long-range axonal connectivity and axonal degeneration. betaII-spectrin-null neurons exhibited reduced axon growth, loss of actin-spectrin-based periodic membrane skeleton, and impaired bidirectional axonal transport of synaptic cargo. We found that betaII-spectrin associates with KIF3A, KIF5B, KIF1A, and dynactin, implicating spectrin in the coupling of motors and synaptic cargo. betaII-spectrin required phosphoinositide lipid binding to promote axonal transport and restore axon growth. Knockout of ankyrin-B (AnkB), a betaII-spectrin partner, primarily impaired retrograde organelle transport, while double knockout of betaII-spectrin and AnkB nearly eliminated transport. Thus, betaII-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. |
