Endophilin 1 is a presynaptically enriched protein which binds the GTPase d
ynamin and the polyphosphoinositide phosphatase synptojanin. Perturbation o
f endophilin function in cell-free systems and in a living synapse has impl
icated endophilin in endocytic vesicle budding (Ringstad, N., H. Gad, P. Lo
w, G. Di Paolo, L. Brodin, O. Shupliakov, and P. De Camilli. 1999. Neuron.
24:143-154; Schmidt, A., M. Wolde, C. Thiele, W. Fest, H. Kratzin, AN. Podt
elejnikov, W. Witke, W.B. Huttner, and H.D. Soling. 1999. Nature. 401:133-1
41; Gad, H., N. Ringstad, P. Low, O. Kjaerulff, J. Gustafsson, M. Wenk, G.
Di Paolo, Y. Nemoto, J. Crun, M.H. Ellisman, et al. 2000. Neuron. 27:301-31
2). Here, we show that purified endophilin can directly bind and evaginate
lipid bilayers into narrow tubules similar in diameter to the neck of a cla
thrin-coated bud, providing new insight into the mechanisms through which e
ndophilin may participate in membrane deformation and vesicle budding. This
property of endophilin is independent of its putative lysophosphatydic aci
d acyl transferase activity, is mediated by its NH2-terminal region, and re
quires an amino acid stretch homologous to a corresponding region in amphip
hysin, a protein previously shown to have similar effects on lipid bilayers
(Takei, K., V.I. Slepnev,V. Haucke, and P. De Camilli. 1999. Nat. Cell Bio
l. 1:33-39). Endophilin cooligomerizes with dynamin rings on lipid tubules
and inhibits dynamin's GTP-dependent vesiculating activity. Endophilin B, a
protein with homology to endophilin 1, partially localizes to the Golgi co
mplex and also deforms lipid bilayers into tubules, underscoring a potentia
l role of endophilin family members in diverse tubulovesicular membrane-tra
fficking events in the cell.