title: ACF7: an essential integrator of microtubule dynamics.
abstract: ACF7 is a member of the spectraplakin family of cytoskeletal crosslinking proteins possessing actin and microtubule binding domains. Here, we show that ACF7 is an essential integrator of MT-actin dynamics. In endodermal cells, ACF7 binds along microtubules but concentrates at their distal ends and at cell borders when polarized. In ACF7's absence, microtubules still bind EB1 and CLIP170, but they no longer grow along polarized actin bundles, nor do they pause and tether to actin-rich cortical sites. The consequences are less stable, long microtubules with skewed cytoplasmic trajectories and altered dynamic instability. In response to wounding, ACF7 null cultures activate polarizing signals, but fail to maintain them and coordinate migration. Rescue of these defects requires ACF7's actin and microtubule binding domains. Thus, spectraplakins are important for controlling microtubule dynamics and reinforcing links between microtubules and polarized F-actin, so that cellular polarization and coordinated cell movements can be sustained.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kodama
authors.forename: Iakowos
authors.initials: I
authors.lastname: Karakesisoglou
authors.forename: Ellen
authors.initials: E
authors.lastname: Wong
authors.forename: Alec
authors.initials: A
authors.lastname: Vaezi
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D004707:Endoderm / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006056:Golgi Apparatus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism / Q000473:pathology; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014945:Wound Healing
chemical_list: D000199:Actins; C405804:EB1 microtubule binding proteins; C490632:Macf1 protein, mouse; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C076744:cytoplasmic linker protein 170