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GSK ‐3α/β‐mediated phosphorylation of CRMP ‐2 regulates activity‐dependent dendritic growth
Author(s) -
Tan Minghui,
Ma Shanshan,
Huang Qiaoying,
Hu Kunhua,
Song Bin,
Li Mingtao
Publication year - 2013
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.12230
Subject(s) - microbiology and biotechnology , gene knockdown , phosphorylation , gsk 3 , chemistry , hippocampal formation , gene silencing , gsk3b , dendritic spine , biology , biochemistry , neuroscience , apoptosis , gene
Neuronal activity shapes the dendritic arbour; however, most of the molecular players in this process remain to be identified. We observed that depolarization‐induced neuronal activity causes an increase in the phosphorylation of glycogen synthase kinase‐3 ( GSK ‐3)α/β on Ser21/9 in cerebellar granule neurons. Using several approaches, including gene knockdown and GSK ‐3α/β S21A/S21A/S9A/S9A double knockin mice, we demonstrated that both GSK ‐3β and GSK ‐3α mediate activity‐dependent dendritic growth and that Ser21/9 phosphorylation of GSK ‐3α/β plays an important role in this process. Collapsin response mediator protein‐2 ( CRMP ‐2), which is crucial for axon development, is phosphorylated at Thr514 and inactivated by GSK ‐3. We found CRMP ‐2 was located mainly in the dendrites of cerebellar granule neurons, in contrast to the axonal distribution in hippocampal neurons. Over‐expression of CRMP ‐2 promoted and knockdown of CRMP ‐2 impaired dendritic growth, suggesting that CRMP ‐2 is necessary and sufficient for activity‐dependent dendritic development. Furthermore, silencing CRMP ‐2 completely blocked the dendritic growth‐promoting effects of GSK ‐3 knockdown, and expression of Thr514 nonphosphorylated form of CRMP ‐2 counteracted the inhibitory effect of constitutively active GSK ‐3. This data indicate that CRMP ‐2 functions downstream of GSK ‐3. Together, these findings identify a novel GSK ‐3/ CRMP ‐2 pathway that connects neuronal activity to dendritic growth.