PMID- 25342295
OWN - NLM
STAT- MEDLINE
DCOM- 20151020
LR  - 20201209
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 5
DP  - 2014 Oct 24
TI  - Arl3 and LC8 regulate dissociation of dynactin from dynein.
PG  - 5295
LID - 10.1038/ncomms6295 [doi]
AB  - Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of 
      vesicles and organelles along microtubules. However, the regulatory mechanism 
      underlying release of dynactin bound cargoes from dynein motor remains largely 
      unknown. Here we report that ADP-ribosylation factor-like 3 (Arl3) and dynein 
      light chain LC8 induce dissociation of dynactin from dynein. Immunoprecipitation 
      and microtubule pull-down assays revealed that Arl3(Q71L) and LC8 facilitated 
      detachment of dynactin from dynein. We also demonstrated Arl3(Q71L) or 
      LC8-mediated dynactin release from a dynein-dynactin complex through trace 
      experiments using quantum dot (Qdot)-conjugated proteins. Furthermore, we 
      disclosed interactions of Arl3 and LC8 with dynactin and dynein, respectively, by 
      live-cell imaging. Finally, knockdown (KD) of Arl3 and LC8 by siRNA induced 
      abnormal localizations of dynein, dynactin and related organelles. Our findings 
      uncovered the surprising functional relevance of GTP-bound Arl3 and LC8 for the 
      unloading regulation of dynactin-bound cargo from dynein motor.
FAU - Jin, Mingyue
AU  - Jin M
AD  - Department of Genetic Disease Research, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
FAU - Yamada, Masami
AU  - Yamada M
AD  - Department of Genetic Disease Research, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
FAU - Arai, Yoshiyuki
AU  - Arai Y
AD  - Department of Biomolecular Science and Engineering, Institute of Scientific and 
      Industrial Research, Osaka University, Mihoga-oka 8-1, Osaka 567-0047, Japan.
FAU - Nagai, Takeharu
AU  - Nagai T
AD  - Department of Biomolecular Science and Engineering, Institute of Scientific and 
      Industrial Research, Osaka University, Mihoga-oka 8-1, Osaka 567-0047, Japan.
FAU - Hirotsune, Shinji
AU  - Hirotsune S
AD  - Department of Genetic Disease Research, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141024
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Dynactin Complex)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Mutant Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Proteins)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 3.6.1.2 (Arl3 protein, mouse)
RN  - EC 3.6.4.2 (Cytoplasmic Dyneins)
RN  - EC 3.6.4.2 (DYNLL1 protein, mouse)
RN  - EC 3.6.4.2 (Dyneins)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
SB  - IM
MH  - ADP-Ribosylation Factors/*metabolism
MH  - Animals
MH  - Cytoplasmic Dyneins
MH  - Dynactin Complex
MH  - Dyneins/*metabolism
MH  - Embryo, Mammalian/cytology
MH  - Fibroblasts/metabolism
MH  - Gene Knockdown Techniques
MH  - Green Fluorescent Proteins/metabolism
MH  - Humans
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Microtubule-Associated Proteins/*metabolism
MH  - Microtubules/metabolism
MH  - Mutant Proteins/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Recombinant Proteins/metabolism
EDAT- 2014/10/25 06:00
MHDA- 2015/10/21 06:00
CRDT- 2014/10/25 06:00
PHST- 2014/07/11 00:00 [received]
PHST- 2014/09/18 00:00 [accepted]
PHST- 2014/10/25 06:00 [entrez]
PHST- 2014/10/25 06:00 [pubmed]
PHST- 2015/10/21 06:00 [medline]
AID - ncomms6295 [pii]
AID - 10.1038/ncomms6295 [doi]
PST - epublish
SO  - Nat Commun. 2014 Oct 24;5:5295. doi: 10.1038/ncomms6295.