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Accueil > Bibliographie > CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 association with (...)

CK2-regulated schwannomin-interacting protein (...)

J Neurochem. 2015 May ; [Epub ahead of print]
CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 association with AnkG contributes to the maintenance of the axon initial segment.
Papandreou MJ, Vacher H, Fache MP, Klingler E, Rueda-Boroni F, Ferracci G, Debarnot C, Piperoglou C, Garcia Del Cano G, Goutebroze L, Dargent B.

The axon initial segment (AIS) plays a central role in electrogenesis and in the maintenance of neuronal polarity. Its molecular organization is dependent on the scaffolding protein ankyrin (Ank) G and is regulated by kinases. For example, the phosphorylation of voltage-gated sodium channels by the protein kinase CK2 regulates their interaction with AnkG and, consequently, their accumulation at the AIS. We previously showed that IQCJ-SCHIP-1, an isoform of the schwannomin-interacting protein 1 (SCHIP-1), accumulated at the AIS in vivo. Here, we analyzed the molecular mechanisms involved in IQCJ-SCHIP-1-specific axonal location. We showed that IQCJ-SCHIP-1 accumulation in the AIS of cultured hippocampal neurons depended on AnkG expression. Pull-down assays and Surface Plasmon Resonance (SPR) analysis demonstrated that AnkG binds to CK2-phosphorylated IQCJ-SCHIP-1 but not to the non-phosphorylated protein. SPR approaches using IQCJ-SCHIP-1, SCHIP-1a, another SCHIP-1 isoform, and their C-terminus tail mutants revealed that a segment including multiple CK2-phosphorylatable sites was directly involved in the interaction with AnkG. Pharmacological inhibition of CK2 diminished both IQCJ-SCHIP-1 and AnkG accumulation in the AIS. Silencing SCHIP-1 expression reduced AnkG cluster at the AIS. Finally, overexpression of IQCJ-SCHIP-1 decreased AnkG concentration at the AIS, whereas a mutant deleted of the CK2-regulated AnkG interaction site did not. Our study reveals that CK2-regulated IQJC-SCHIP-1 association with AnkG contributes to AIS maintenance. This article is protected by copyright. All rights reserved.

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