Impact of JNK and Its Substrates on Dendritic Spine Morphology

Cells

Hasan Mohammad¹  Artemis Varidaki¹  Christel Sourander¹  EleanorT. Coffey¹  Emilia Komulainen¹  Heikki Rauvala²  Natalia Kulesskaya² 

[1] Turku Bioscience, University of Turku and Åbo Akademi University, Tykistokatu 6, 20500 Turku, Finland;University of Helsinki, Neuroscience Center, 00014 Helsinki, Finland;

关键词: jnk1;    jnk;    synaptic plasticity;    dendritic spine;    substrate;    hippocampus;    dcx;    marcksl1;    mrp;    morris water maze;   

DOI  :  10.3390/cells9020440

来源: DOAJ

【 摘 要 】

The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and Jnk1-/- mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking Jnk1-/- using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, Jnk1-/- mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.

【 授权许可】

Unknown