RT Journal Article
SR Electronic
T1 Neurexins play a crucial role in cerebellar granule cell survival by organizing autocrine machinery for neurotrophins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.14.383158
DO 10.1101/2020.11.14.383158
A1 Takeshi Uemura
A1 Emi Suzuki
A1 Shiori Kawase
A1 Taiga Kurihara
A1 Misato Yasumura
A1 Tomoyuki Yoshida
A1 Shuya Fukai
A1 Maya Yamazaki
A1 Peng Fei
A1 Manabu Abe
A1 Masahiko Watanabe
A1 Kenji Sakimura
A1 Masayoshi Mishina
A1 Katsuhiko Tabuchi
YR 2020
UL http://biorxiv.org/content/early/2020/11/15/2020.11.14.383158.abstract
AB Neurexins (NRXNs) are among the key presynaptic cell adhesion molecules that regulate synapse function and formation via trans-synaptic interaction with postsynaptic ligands. Here, we generated cerebellar granule cell (CGC)-specific Nrxn triple-knockout (TKO) mice to allow the deletion of all NRXNs. Unexpectedly, most CGCs died in these mice. The requirement of NRNXs for cell survival was reproduced in cultured CGCs. We showed that the axons of cultured Nrxn TKO CGCs that were not in contact with the postsynaptic structure had defects in the formation of presynaptic protein cluster and action potential-induced Ca2+ influx. Additionally, these cells were impaired in the secretion from axons of depolarization-induced fluorescence-tagged brain-derived neurotrophic factor (BDNF), and the cell-survival defect was rescued by the application of BDNF. Our results suggest that CGC survival is maintained by autocrine neurotrophic factors, and that NRXNs organize the presynaptic protein clusters and the autocrine neurotrophic factor secretory machinery independent of contact with postsynaptic ligands.Competing Interest StatementThe authors have declared no competing interest.