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Involvement of α2‐antiplasmin in dendritic growth of hippocampal neurons
Author(s) -
Kawashita Eri,
Kanno Yosuke,
Asayama Haruka,
Okada Kiyotaka,
Ueshima Shigeru,
Matsuo Osamu,
Matsuno Hiroyuki
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.12281
Subject(s) - hippocampal formation , plasmin , microbiology and biotechnology , filopodia , biology , neurite , neuroscience , neurogenesis , in vitro , actin , biochemistry , enzyme
The α2‐Antiplasmin (α2 AP ) protein is known as a principal physiological inhibitor of plasmin, but we previously demonstrated that it acts as a regulatory factor for cellular functions independent of plasmin. α2 AP is highly expressed in the hippocampus, suggesting a potential role for α2 AP in hippocampal neuronal functions. However, the role for α2 AP was unclear. This study is the first to investigate the involvement of α2 AP in the dendritic growth of hippocampal neurons. The expression of microtubule‐associated protein 2, which contributes to neurite initiation and neuronal growth, was lower in the neurons from α2 AP −/− mice than in the neurons from α2 AP +/+ mice. Exogenous treatment with α2 AP enhanced the microtubule‐associated protein 2 expression, dendritic growth and filopodia formation in the neurons. This study also elucidated the mechanism underlying the α2 AP ‐induced dendritic growth. Aprotinin, another plasmin inhibitor, had little effect on the dendritic growth of neurons, and α2 AP induced its expression in the neurons from plaminogen −/− mice. The activation of p38 MAPK was involved in the α2 AP ‐induced dendritic growth. Therefore, our findings suggest that α2 AP induces dendritic growth in hippocampal neurons through p38 MAPK activation, independent of plasmin, providing new insights into the role of α2 AP in the CNS .