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Neurosci Lett. 2008 May 30;437(2):111-5. doi: 10.1016/j.neulet.2008.03.083. Epub 2008 Apr 3.

Dynein cleavage and microtubule accumulation in okadaic acid-treated neurons.

Author information

1
Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.

Abstract

Impairment of protein phosphatase 2A (PP2A) activity is implicated in tau hyperphosphorylation and microtubule (MT) instability in Alzheimer's disease (AD). Here, we report that okadaic acid, an effective PP2A inhibitor, suppresses the levels of acetylated and detyrosinated tubulins, but enhances tyrosinated tubulins in rat primary cortical neuron cultures. Immunocytochemistry experiments reveal that MTs accumulate intensely around soma and proximal neurites, implying impairment of MT transport to distal neurites which is mediated by dynein and dynactin. Here, we reveal that they can be cleaved by calpain. Notably, shortening of process length in OA-treated neurons is alleviated when calpain cleavage activity is inhibited. Based on these results, we propose that calpain-mediated dynein cleavage in OA-treated neurons is responsible for the MT transport deficit, and consequently, neurite retraction.

PMID:
18448253
DOI:
10.1016/j.neulet.2008.03.083
[Indexed for MEDLINE]

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