title: ZF21 protein regulates cell adhesion and motility.
abstract: Cell migration on an extracellular matrix (ECM) requires continuous formation and turnover of focal adhesions (FAs) along the direction of cell movement. However, our knowledge of the components of FAs and the mechanism of their regulation remains limited. Here, we identify ZF21, a member of a protein family characterized by the presence of a phosphatidylinositol 3-phosphate-binding FYVE domain, to be a new regulator of FAs and cell movement. Knockdown of ZF21 expression in cells increased the number of FAs and suppressed cell migration. Knockdown of ZF21 expression also led to a significant delay in FA disassembly following induction of synchronous disassembly of FAs by nocodazole treatment. ZF21 bound to focal adhesion kinase, localized to FAs, and was necessary for dephosphorylation of FAK at Tyr(397), which is important for disassembly of FAs. Thus, ZF21 represents a new component of FAs, mediates disassembly of FAs, and thereby regulates cell motility.
authors.affiliation: Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hoshino
authors.forename: Takeharu
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Naohiko
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D005109:Extracellular Matrix / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C108257:ITGB1BP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C426003:ZFYVE1 protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human