| First Author | Yang R | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 30 | Pages | 15262-15271 |
| PubMed ID | 31285321 | Mgi Jnum | J:277752 |
| Mgi Id | MGI:6333048 | Doi | 10.1073/pnas.1904348116 |
| Citation | Yang R, et al. (2019) ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity. Proc Natl Acad Sci U S A 116(30):15262-15271 |
| abstractText | Giant ankyrin-B (ankB) is a neurospecific alternatively spliced variant of ANK2, a high-confidence autism spectrum disorder (ASD) gene. We report that a mouse model for human ASD mutation of giant ankB exhibits increased axonal branching in cultured neurons with ectopic CNS axon connectivity, as well as with a transient increase in excitatory synapses during postnatal development. We elucidate a mechanism normally limiting axon branching, whereby giant ankB localizes to periodic axonal plasma membrane domains through L1 cell-adhesion molecule protein, where it couples microtubules to the plasma membrane and prevents microtubule entry into nascent axon branches. Giant ankB mutation or deficiency results in a dominantly inherited impairment in selected communicative and social behaviors combined with superior executive function. Thus, gain of axon branching due to giant ankB-deficiency/mutation is a candidate cellular mechanism to explain aberrant structural connectivity and penetrant behavioral consequences in mice as well as humans bearing ASD-related ANK2 mutations. |
