TY - JOUR
T1 - Live-cell imaging in Caenorhabditis elegans reveals the distinct roles of dynamin self-assembly and guanosine triphosphate hydrolysis in the removal of apoptotic cells
AU - He, Bin
AU - Yu, Xiaomeng
AU - Margolis, Moran
AU - Liu, Xianghua
AU - Leng, Xiaohong
AU - Etzion, Yael
AU - Zheng, Fei
AU - Lu, Nan
AU - Quiocho, Florante A.
AU - Danino, Dganit
AU - Zhou, Zheng
PY - 2010/2/15
Y1 - 2010/2/15
N2 - Dynamins are large GTPases that oligomerize along membranes. Dynamin's membrane fission activity is believed to underlie many of its physiological functions in membrane trafficking. Previously, we reported that DYN-1 (Caenorhabditis elegans dynamin) drove the engulfment and degradation of apoptotic cells through promoting the recruitment and fusion of intracellular vesicles to phagocytic cups and phagosomes, an activity distinct from dynamin's well-known membrane fission activity. Here, we have detected the oligomerization of DYN-1 in living C. elegans embryos and identified DYN-1 mutations that abolish DYN-1's oligomerization or GTPase activities. Specifically, abolishing selfassembly destroys DYN-1's association with the surfaces of extending pseudopods and maturing phagosomes, whereas inactivating guanosine triphosphate (GTP) binding blocks the dissociation of DYN-1 from these membranes. Abolishing the self-assembly or GTPase activities of DYN-1 leads to common as well as differential phagosomal maturation defects. Whereas both types of mutations cause delays in the transient enrichment of the RAB-5 GTPase to phagosomal surfaces, only the self-assembly mutation but not GTP binding mutation causes failure in recruiting the RAB-7 GTPase to phagosomal surfaces. We propose that during cell corpse removal, dynamin's self-assembly and GTP hydrolysis activities establish a precise dynamic control of DYN-1's transient association to its target membranes and that this control mechanism underlies the dynamic recruitment of downstream effectors to target membranes.
AB - Dynamins are large GTPases that oligomerize along membranes. Dynamin's membrane fission activity is believed to underlie many of its physiological functions in membrane trafficking. Previously, we reported that DYN-1 (Caenorhabditis elegans dynamin) drove the engulfment and degradation of apoptotic cells through promoting the recruitment and fusion of intracellular vesicles to phagocytic cups and phagosomes, an activity distinct from dynamin's well-known membrane fission activity. Here, we have detected the oligomerization of DYN-1 in living C. elegans embryos and identified DYN-1 mutations that abolish DYN-1's oligomerization or GTPase activities. Specifically, abolishing selfassembly destroys DYN-1's association with the surfaces of extending pseudopods and maturing phagosomes, whereas inactivating guanosine triphosphate (GTP) binding blocks the dissociation of DYN-1 from these membranes. Abolishing the self-assembly or GTPase activities of DYN-1 leads to common as well as differential phagosomal maturation defects. Whereas both types of mutations cause delays in the transient enrichment of the RAB-5 GTPase to phagosomal surfaces, only the self-assembly mutation but not GTP binding mutation causes failure in recruiting the RAB-7 GTPase to phagosomal surfaces. We propose that during cell corpse removal, dynamin's self-assembly and GTP hydrolysis activities establish a precise dynamic control of DYN-1's transient association to its target membranes and that this control mechanism underlies the dynamic recruitment of downstream effectors to target membranes.
UR - http://www.scopus.com/inward/record.url?scp=76649095298&partnerID=8YFLogxK
U2 - 10.1091/mbc.E09-05-0440
DO - 10.1091/mbc.E09-05-0440
M3 - 文章
C2 - 20016007
AN - SCOPUS:76649095298
SN - 1059-1524
VL - 21
SP - 610
EP - 629
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 4
ER -