Ankyrin G Membrane Partners Drive the Establishment and Maintenance of the Axon Initial Segment

The axon initial segment (AIS) is a highly specialized neuronal compartment that plays a key role in neuronal development and excitability. It concentrates multiple membrane proteins such as ion channels and cell adhesion molecules (CAMs) that are recruited to the AIS by the scaffold protein ankyrin...

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Published inFrontiers in cellular neuroscience Vol. 11; p. 6
Main Authors Leterrier, Christophe, Clerc, Nadine, Rueda-Boroni, Fanny, Montersino, Audrey, Dargent, Bénédicte, Castets, Francis
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 26.01.2017
Frontiers
Frontiers Media S.A
Subjects
Ankyrins
Brain slice preparation
Cell adhesion & migration
Cell adhesion molecules
Cortex
Excitability
Hippocampus
Ion channels
Kinases
Life Sciences
Membrane proteins
Neurobiology
Neurons
Neurons and Cognition
Neuroscience
Plasmids
Polyclonal antibodies
Proteins
Sodium
Sodium channels (voltage-gated)
axon initial segment
cultured hippocampal neurons
neurofascin-186
organotypic slices
ankyrin G
voltage gated sodium channel
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Summary:The axon initial segment (AIS) is a highly specialized neuronal compartment that plays a key role in neuronal development and excitability. It concentrates multiple membrane proteins such as ion channels and cell adhesion molecules (CAMs) that are recruited to the AIS by the scaffold protein ankyrin G (ankG). The crucial function of ankG in the anchoring of AIS membrane components is well established, but a reciprocal role of membrane partners in ankG targeting and stabilization remained elusive. In rat cultured hippocampal neurons and cortical organotypic slices, we found that shRNA-mediated knockdown of ankG membrane partners (voltage-gated sodium channels (Nav) or neurofascin-186) led to a decrease of ankG concentration and perturbed the AIS formation and maintenance. These effects were rescued by expressing a recombinant AIS-targeted Nav or by a minimal construct containing the ankyrin-binding domain of Nav1.2 and a membrane anchor (mABD). Moreover, overexpressing mABD in mature neurons led to ankG mislocalization. Altogether, these results demonstrate that a tight and precocious association of ankG with its membrane partners is a key step for the establishment and maintenance of the AIS.
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Edited by: Maren Engelhardt, Heidelberg University, Germany
Present address: Nadine Clerc, Aix Marseille University, CNRS, IBDM, Marseille, France
Reviewed by: Daniela Mauceri, Heidelberg University, Germany; Vann Bennett, Howard Hughes Medical Institute, USA
These authors have contributed equally to this work.
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2017.00006