Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis.
The conserved FER-CIP4 homology (FCH) domain is found in the pombe Cdc15 homology (PCH) protein family members, including formin-binding protein 17 (FBP17). However, the amino acid sequence homology extends beyond the FCH domain. We have termed this region the extended FC (EFC) domain. We found that FBP17 coordinated membrane deformation with actin cytoskeleton reorganization during endocytosis. The EFC domains of FBP17, CIP4, and other PCH protein family members show weak homology to the Bin-amphiphysin-Rvs (BAR) domain. The EFC domains bound strongly to phosphatidylserine and phosphatidylinositol 4,5-bisphosphate and deformed the plasma membrane and liposomes into narrow tubules. Most PCH proteins possess an SH3 domain that is known to bind to dynamin and that recruited and activated neural Wiskott-Aldrich syndrome protein (N-WASP) at the plasma membrane. FBP17 and/or CIP4 contributed to the formation of the protein complex, including N-WASP and dynamin-2, in the early stage of endocytosis. Furthermore, knockdown of endogenous FBP17 and CIP4 impaired endocytosis. Our data indicate that PCH protein family members couple membrane deformation to actin cytoskeleton reorganization in various cellular processes.
Tsujita
Kazuya
K
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639 Japan.
Suetsugu
Shiro
S
Sasaki
Nobunari
N
Furutani
Masahiro
M
Oikawa
Tsukasa
T
Takenawa
Tadaomi
T
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism*; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism
D000199:Actins; D002352:Carrier Proteins; C433770:FNBP1 protein, human; D050556:Fatty Acid-Binding Proteins; D008081:Liposomes; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D066246:ErbB Receptors; D034285:Dynamin II