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CK 2‐regulated schwannomin‐interacting protein IQCJ ‐ SCHIP ‐1 association with AnkG contributes to the maintenance of the axon initial segment
Author(s) -
Papandréou MarieJeanne,
Vacher Hélène,
Fache MariePierre,
Klingler Esther,
RuedaBoroni Fanny,
Ferracci Géraldine,
Debarnot Claire,
Pipéroglou Christelle,
Del Caño Gontzal Garcia,
Goutebroze Laurence,
Dargent Bénédicte
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13158
Subject(s) - phosphorylation , biology , microbiology and biotechnology , scaffold protein , kinase , signal transduction
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 CK 2 regulates their interaction with AnkG and, consequently, their accumulation at the AIS . We previously showed that IQ motif containing J‐Schwannomin‐Interacting Protein 1 ( IQCJ ‐ SCHIP ‐1), an isoform of the 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 analysis demonstrated that AnkG binds to CK 2‐phosphorylated IQCJ ‐ SCHIP ‐1 but not to the non‐phosphorylated protein. Surface plasmon resonance approaches using IQCJ ‐ SCHIP ‐1, SCHIP ‐1a, another SCHIP ‐1 isoform, and their C‐terminus tail mutants revealed that a segment including multiple CK 2‐phosphorylatable sites was directly involved in the interaction with AnkG. Pharmacological inhibition of CK 2 diminished both IQCJ ‐ SCHIP ‐1 and AnkG accumulation in the AIS . Silencing SCHIP ‐1 expression reduced AnkG cluster at the AIS . Finally, over‐expression of IQCJ ‐ SCHIP ‐1 decreased AnkG concentration at the AIS , whereas a mutant deleted of the CK 2‐regulated AnkG interaction site did not. Our study reveals that CK 2‐regulated IQJC ‐ SCHIP ‐1 association with AnkG contributes to AIS maintenance.The axon initial segment ( AIS ) organization depends on ankyrin (Ank) G and kinases. Here we showed that AnkG binds to CK 2‐phosphorylated IQCJ ‐ SCHIP ‐1, in a segment including 12 CK 2‐phosphorylatable sites. In cultured neurons, either pharmacological inhibition of CK 2 or IQCJ ‐ SCHIP ‐1 silencing reduced AnkG clustering. Overexpressed IQCJ ‐ SCHIP ‐1 decreased AnkG concentration at the AIS whereas a mutant deleted of the CK 2‐regulated AnkG interaction site did not. Thus, CK 2‐regulated IQJC ‐ SCHIP ‐1 association with AnkG contributes to AIS maintenance.