TY - JOUR
T1 - Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes.
AU - Kimura, Shunsuke
AU - Noda, Takeshi
AU - Yoshimori, Tamotsu
PY - 2008
Y1 - 2008
N2 - Autophagy is a membrane trafficking pathway that carries cytosolic components to the lysosome for degradation. During this process, the autophagosome, a double-membraned organelle, is generated de novo, sequesters cytoplasmic proteins and organelles, and delivers them to lysosomes. However, the mechanism by which autophagosomes are targeted to lysosomes has not been determined. Here, we observed the real-time behavior of microtubule-associated protein light chain 3 (LC3), which localizes to autophagosomes, and showed that autophagosomes move in a microtubule- and dynein-dynactin motor complex-dependent manner. After formation, autophagosomes show a rapid vectorial movement in the direction of the centrosome, where lysosomes are usually concentrated. Microinjection of antibodies against LC3 inhibited this movement; furthermore, using FRAP, we showed that anti-LC3 antibody injection caused a defect in targeting of autophagosomes to lysosomes. Collectively, our data demonstrate the functional significance of autophagosome movement that enables effective delivery from the cytosol to lysosomes.
AB - Autophagy is a membrane trafficking pathway that carries cytosolic components to the lysosome for degradation. During this process, the autophagosome, a double-membraned organelle, is generated de novo, sequesters cytoplasmic proteins and organelles, and delivers them to lysosomes. However, the mechanism by which autophagosomes are targeted to lysosomes has not been determined. Here, we observed the real-time behavior of microtubule-associated protein light chain 3 (LC3), which localizes to autophagosomes, and showed that autophagosomes move in a microtubule- and dynein-dynactin motor complex-dependent manner. After formation, autophagosomes show a rapid vectorial movement in the direction of the centrosome, where lysosomes are usually concentrated. Microinjection of antibodies against LC3 inhibited this movement; furthermore, using FRAP, we showed that anti-LC3 antibody injection caused a defect in targeting of autophagosomes to lysosomes. Collectively, our data demonstrate the functional significance of autophagosome movement that enables effective delivery from the cytosol to lysosomes.
UR - http://www.scopus.com/inward/record.url?scp=47149089713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47149089713&partnerID=8YFLogxK
U2 - 10.1247/csf.08005
DO - 10.1247/csf.08005
M3 - Article
C2 - 18388399
AN - SCOPUS:47149089713
SN - 0386-7196
VL - 33
SP - 109
EP - 122
JO - Cell Structure and Function
JF - Cell Structure and Function
IS - 1
ER -