WAFL, a new protein involved in regulation of early endocytic transport at the intersection of actin and microtubule dynamics.
We have previously identified a new gene with sequence homology to the WASP-family of actin regulators denoted WAFL (WASP and FKBP-like). Here we report a possible biological function for WAFL, by demonstrating an association to early endosomes via its central coiled-coil domain. Further we show by functional and structural studies that WAFL is associated with both microtubules and the actin filament system, the two means of transport of early endosomes. In addition, WAFL interacts with WASP-interacting protein (WIP) and actin, thus linking WAFL to actin dynamics. The use of RNAi depletion of WAFL shows that WAFL-deficient cells display delayed transport of endosomal cargo. Our findings are compatible with a model whereby WAFL is involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement.
Viklund
Ing-Marie
IM
Strategic Research Center IRIS, Karolinska Institute, Stockholm, Sweden.
Aspenström
Pontus
P
Meas-Yedid
Vannary
V
Zhang
Bo
B
Kopec
Jolanta
J
Agren
Daniel
D
Schneider
Gunter
G
D'Amato
Mauro
M
Olivo-Marin
Jean-Christophe
JC
Sansonetti
Philippe
P
Van Nhieu
Guy Tran
GT
Pettersson
Sven
S
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053778:Thiazolidines / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; C512703:FKBP133 protein, mouse; C540489:FKBP15 protein, human; D011993:Recombinant Fusion Proteins; D053778:Thiazolidines; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D022021:Tacrolimus Binding Proteins; C037067:latrunculin A