Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits.
The GTPase dynamin, a key player in endocytic membrane fission, interacts with numerous proteins that regulate actin dynamics and generate/sense membrane curvature. To determine the functional relationship between these proteins and dynamin, we have analyzed endocytic intermediates that accumulate in cells that lack dynamin (derived from dynamin 1 and 2 double conditional knockout mice). In these cells, actin-nucleating proteins, actin, and BAR domain proteins accumulate at the base of arrested endocytic clathrin-coated pits, where they support the growth of dynamic long tubular necks. These results, which we show reflect the sequence of events in wild-type cells, demonstrate a concerted action of these proteins prior to, and independent of, dynamin and emphasize similarities between clathrin-mediated endocytosis in yeast and higher eukaryotes. Our data also demonstrate that the relationship between dynamin and actin is intimately connected to dynamin's endocytic role and that dynamin terminates a powerful actin- and BAR protein-dependent tubulating activity.
Ferguson
Shawn M
SM
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Ferguson
Shawn
S
Raimondi
Andrea
A
Paradise
Summer
S
Shen
Hongying
H
Mesaki
Kumi
K
Ferguson
Agnes
A
Destaing
Olivier
O
Ko
Genevieve
G
Takasaki
Junko
J
Cremona
Ottavio
O
O' Toole
Eileen
E
De Camilli
Pietro
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D055786:Gene Knockout Techniques; D051379:Mice; D018345:Mice, Knockout
D000199:Actins; D002966:Clathrin; D034284:Dynamin I; D034285:Dynamin II