PMID- 30366015
OWN - NLM
STAT- MEDLINE
DCOM- 20190311
LR  - 20190311
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 690
DP  - 2019 Jan 18
TI  - p150(glued) deficiency impairs effective fusion between autophagosomes and 
      lysosomes due to their redistribution to the cell periphery.
PG  - 181-187
LID - S0304-3940(18)30712-2 [pii]
LID - 10.1016/j.neulet.2018.10.036 [doi]
AB  - Dynein-dynactin has an indispensable role in autophagy and p150(glued) is the 
      largest component of the dynactin complex. Here, we characterized the effects of 
      knockdown (KD) of endogenous p150(glued) and of the pathogenic mutation of 
      p150(glued) found in autosomal dominant p150(glued)-associated disorders 
      [hereditary motor neuronopathy with vocal paresis (HMN7B) and Perry syndrome] on 
      autophagy. Overexpression of the p150(glued) pathogenic mutant or siRNA KD of 
      p150(glued) promoted the localization of lysosomes at the cell periphery and 
      increased the number of autophagosomes, suggesting partial blockage of autophagic 
      flux. Surprisingly, although autophagosomes and lysosomes were redistributed 
      predominantly to the cell periphery in p150(glued)-KD cells, the autolysosome 
      formation ratio was preserved. However, under autophagy activation conditions 
      induced by starvation, the ratio of autophagosome-lysosome fusion in 
      p150(glued)-KD cells was decreased in the early phase. Our data demonstrate that 
      functional loss of p150(glued) may cause autophagic insufficiency, which may be 
      associated with the pathogenesis of p150(glued)-associated disorders.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Ishikawa, Kei-Ichi
AU  - Ishikawa KI
AD  - Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan.
FAU - Saiki, Shinji
AU  - Saiki S
AD  - Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan; Division of Development of Autophagy 
      Modulating Drugs, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address: ssaiki@juntendo.ac.jp.
FAU - Furuya, Norihiko
AU  - Furuya N
AD  - Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan; Division of Development of Autophagy 
      Modulating Drugs, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan.
FAU - Imamichi, Yoko
AU  - Imamichi Y
AD  - Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan.
FAU - Tsuboi, Yoshio
AU  - Tsuboi Y
AD  - Department of Neurology, Fukuoka University School of Medicine, 7-45-1, Nanakuma, 
      Jonan-Ku, Fukuoka, 814-0180, Japan.
FAU - Hattori, Nobutaka
AU  - Hattori N
AD  - Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan; Division of Development of Autophagy 
      Modulating Drugs, Juntendo University School of Medicine, 2-1-1, Hongo, 
      Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address: nhattori@juntendo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181023
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Dynactin Complex)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Autophagosomes/*metabolism
MH  - Cell Line, Tumor
MH  - Dynactin Complex/genetics/*metabolism
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Lysosomes/*metabolism
MH  - Mutation/genetics
MH  - Protein Subunits/genetics/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Up-Regulation
OTO - NOTNLM
OT  - Autophagosome
OT  - Autophagy
OT  - Dynactin
OT  - Lysosome
OT  - P150(glued)
OT  - Perry syndrome
EDAT- 2018/10/27 06:00
MHDA- 2019/03/12 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/07/09 00:00 [received]
PHST- 2018/10/10 00:00 [revised]
PHST- 2018/10/16 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2019/03/12 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - S0304-3940(18)30712-2 [pii]
AID - 10.1016/j.neulet.2018.10.036 [doi]
PST - ppublish
SO  - Neurosci Lett. 2019 Jan 18;690:181-187. doi: 10.1016/j.neulet.2018.10.036. Epub 
      2018 Oct 23.