RRC ID 77499
Author Minegishi T, Uesugi Y, Kaneko N, Yoshida W, Sawamoto K, Inagaki N.
Title Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration.
Journal Cell Rep
Abstract As an essential step for brain morphogenesis, neurons migrate via mechanical interactions with components of their environment such as neighboring cells and the extracellular matrix. However, the molecular mechanism by which neurons exert forces on their environment during migration remains poorly understood. Here, we show that shootin1b is expressed in migrating mouse olfactory interneurons and accumulates at their leading process growth cone. We demonstrate that shootin1b, by binding to cortactin and L1-CAM, couples F-actin retrograde flow and the adhesive substrate as a clutch molecule. Shootin1b-mediated clutch coupling at the growth cone generates traction force on the substrate, thereby promoting leading process extension and subsequent somal translocation of olfactory interneurons. Furthermore, loss of shootin1 causes abnormal positioning of the interneurons and dysgenesis of the olfactory bulb. Our findings indicate that shootin1b plays a key role in force-driven leading process extension, which propels the migration of olfactory interneurons during olfactory bulb formation.
Volume 25(3)
Pages 624-639.e6
Published 2018-10-16
DOI 10.1016/j.celrep.2018.09.068
PII S2211-1247(18)31528-6
PMID 30332643
MeSH Actins / metabolism Animals Brain / cytology Brain / physiology* Cell Adhesion Cell Movement* Cells, Cultured Female Growth Cones / physiology* Interneurons / cytology Interneurons / physiology* Male Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Knockout Nerve Tissue Proteins / physiology* Olfactory Bulb / cytology Olfactory Bulb / physiology* Rats, Wistar
IF 8.109
DNA material pGEX-shootin1b (RDB19937) pCMV-myc-shootin1b (RDB19938)