INF1 is a novel microtubule-associated formin.
Formin proteins, characterized by the presence of conserved formin homology (FH) domains, play important roles in cytoskeletal regulation via their abilities to nucleate actin filament formation and to interact with multiple other proteins involved in cytoskeletal regulation. The C-terminal FH2 domain of formins is key for actin filament interactions and has been implicated in playing a role in interactions with microtubules. Inverted formin 1 (INF1) is unusual among the formin family in having the conserved FH1 and FH2 domains in its N-terminal half, with its C-terminal half being composed of a unique polypeptide sequence. In this study, we have examined a potential role for INF1 in regulating microtubule structure. INF1 associates discretely with microtubules, and this association is dependent on a novel C-terminal microtubule-binding domain. INF1 expressed in fibroblast cells induced actin stress fiber formation, coalignment of microtubules with actin filaments, and the formation of bundled, acetylated microtubules. Endogenous INF1 showed an association with acetylated microtubules, and knockdown of INF1 resulted in decreased levels of acetylated microtubules. Our data suggests a role for INF1 in microtubule modification and potentially in coordinating microtubule and F-actin structure.
Young
Kevin G
KG
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada, K1H 8M5.
Thurston
Susan F
SF
Copeland
Sarah
S
Smallwood
Chelsea
C
Copeland
John W
JW
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D053778:Thiazolidines / Q000378:metabolism; D014018:Tissue Distribution
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D053778:Thiazolidines; D011494:Protein Kinases; C405628:serum response factor kinase; D015739:Nocodazole; C037067:latrunculin A