Tuba, a GEF for CDC42, links dynamin to actin regulatory proteins.
Tuba is a 178kD protein containing four NH2-terminal SH3 domains, a central Dbl homology (DH) domain followed by a BAR domain, and two COOH-terminal SH3 domains. The four NH2-terminal SH3 domains bind the GTPase dynamin, a protein critical for the fission of endocytic vesicles. The DH domain functions as a CDC42-specific guanine nucleotide exchange factor and is unique among DH domains because it is followed by a BAR domain rather than a PH domain. The COOH-terminal SH3 domain binds directly to N-WASP and Ena/VASP proteins, key regulatory proteins of the actin cytoskeleton, and recruits a larger protein complex comprising additional actin regulatory factors. The properties of Tuba provide new evidence for a functional link between dynamin, endocytosis, and actin. The presence of a BAR domain, rather than a PH domain, may reflect its action at high curvature regions of the plasma membrane. Its multiple binding sites for dynamin generate an exceptionally high avidity for this GTPase and make the NH2-terminal region of Tuba a very useful tool for the one-step purification of dynamin.
Cestra
Gianluca
G
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
Kwiatkowski
Adam
A
Salazar
Marco
M
Gertler
Frank
F
De Camilli
Pietro
P
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000502:physiology*; D034281:Dynamins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D018909:src Homology Domains
D000199:Actins; D003598:Cytoskeletal Proteins; C482331:DNMBP protein, human; D020662:Guanine Nucleotide Exchange Factors; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D020764:cdc42 GTP-Binding Protein; D034281:Dynamins