Dyrk1A-mediated phosphorylation of RCAN1 promotes the formation of insoluble RCAN1 aggregates.

Abstract:

:The mechanisms underlying aggregate formation in age-related neurodegenerative diseases remain not well understood. Here we investigated whether dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) is involved in the formation of regulator of calcineurin 1 (RCAN1) aggregates. We show that RCAN1 self-associates and forms multimers, and that this process is promoted by the Dyrk1A-mediated phosphorylation of RCAN1 at the Thr(192) residue. Transgenic mice that overexpress the Dyrk1A exhibited lower levels of phospho-Thr(192)-RCAN1 in 10-month-old-group compared to littermate controls, when analyzed with soluble hippocampus lysates. These results suggest that the phosphorylation of RCAN1 by Dyrk1A stimulates the formation of insoluble aggregates upon aging.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Song WJ,Song EA,Choi SH,Baik HH,Jin BK,Kim JH,Chung SH

doi

10.1016/j.neulet.2013.08.066

subject

Has Abstract

pub_date

2013-10-25 00:00:00

pages

135-40

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(13)00799-4

journal_volume

554

pub_type

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