RT Journal Article
SR Electronic
T1 Ankyrin G membrane partners drive the establishment and maintenance of the axon initial segment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 073163
DO 10.1101/073163
A1 Christophe Leterrier
A1 Nadine Clerc
A1 Fanny Rueda-Boroni
A1 Audrey Montersino
A1 Bénédicte Dargent
A1 Francis Castets
YR 2016
UL http://biorxiv.org/content/early/2016/09/02/073163.abstract
AB The axon initial segment (AIS) is a specialized neuronal compartment that plays a key role in neuronal development and excitability. It concentrates multiple ion channels and cell adhesion molecules. The anchoring of these AIS membrane components is known to be highly dependent of the scaffold protein ankyrin G (ankG) but whether ankG membrane partners play a reciprocal role in ankG targeting and stabilization has not been studied yet. In cultured hippocampal neurons and cortical organotypic slices, we found that shRNA-mediated knockdown of ankG membrane partners led to a decrease of ankG concentration and perturbed the AIS formation and maintenance. These perturbations were rescued by expressing an AIS-targeted sodium channel, or a minimal construct containing the ankyrin-binding domain of Nav1.2 and a membrane anchor. We thus demonstrate that a tight and precocious association of ankG to its membrane partners is crucial for the establishment and maintenance of the AIS.