PMID- 19909785
OWN - NLM
STAT- MEDLINE
DCOM- 20100406
LR  - 20161125
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 468
IP  - 3
DP  - 2010 Jan 14
TI  - PINK1 gene knockdown leads to increased binding of parkin with actin filament.
PG  - 272-6
LID - 10.1016/j.neulet.2009.11.011 [doi]
AB  - Mutations in the PINK1 gene are known to cause early onset familial Parkinson's 
      disease (PD). Genetic fruit fly model studies and rescue experiments with parkin 
      overexpression suggest that PINK1 and parkin are associated via an unidentified 
      mechanism. To gain additional insight into this interaction, we have investigated 
      the impact of PINK1 deficiency on the biological function of parkin using actin 
      filament dynamics. Actin is known to be associated with parkin and is a key 
      regulator of eukaryotic cell death. PINK1 gene knockdown (KD) significantly 
      increased actin aggregation and its binding with parkin. Known PD-related 
      pathological conditions, such as oxidative stress and mitochondrial dysfunction, 
      also increased actin aggregation and parkin binding. PINK1 KD resulted in the 
      increased phosphorylation of cofilin, a protein important for the remodeling of 
      actin filament and neurodegeneration. These results suggest that altered actin 
      dynamics and increased association of parkin with actin filament might underlie 
      the pathological conditions resulting from PINK1 deficiency.
CI  - Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
FAU - Kim, Kyung-Hee
AU  - Kim KH
AD  - Laboratory of Neuroprotection, Division of Life & Pharmaceutical Sciences, Brain 
      Disease Research Institute, College of Pharmacy, Ewha Woman's University, Seoul, 
      South Korea.
FAU - Son, Jin H
AU  - Son JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091110
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (PTEN-induced putative kinase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Actin Cytoskeleton/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Dopamine/metabolism
MH  - Gene Knockdown Techniques
MH  - Mice
MH  - Neurons/metabolism
MH  - Protein Binding
MH  - Protein Kinases/biosynthesis/*genetics
MH  - Ubiquitin-Protein Ligases/*metabolism
EDAT- 2009/11/17 06:00
MHDA- 2010/04/07 06:00
CRDT- 2009/11/14 06:00
PHST- 2009/09/18 00:00 [received]
PHST- 2009/10/27 00:00 [revised]
PHST- 2009/11/05 00:00 [accepted]
PHST- 2009/11/14 06:00 [entrez]
PHST- 2009/11/17 06:00 [pubmed]
PHST- 2010/04/07 06:00 [medline]
AID - S0304-3940(09)01477-3 [pii]
AID - 10.1016/j.neulet.2009.11.011 [doi]
PST - ppublish
SO  - Neurosci Lett. 2010 Jan 14;468(3):272-6. doi: 10.1016/j.neulet.2009.11.011. Epub 
      2009 Nov 10.