title: Dynamic remodeling of the actin cytoskeleton by FMNL1γ is required for structural maintenance of the Golgi complex.
abstract: Formin-like 1 (FMNL1) is a member of the formin family of actin nucleators, and is one of the few formins for which in vitro activities have been well characterized. However, the functional roles of this mammalian formin remain ill-defined. In particular, it is unclear how the unique in vitro biochemical properties of FMNL1 relate to its regulation of cellular processes. Here, we demonstrate that FMNL1 depletion caused a dramatic increase in cellular F-actin content, which resulted in Golgi complex fragmentation. Moreover, increased F-actin and maintenance of Golgi structure were distinctly regulated by the gamma isoform of FMNL1, which required binding to actin. Importantly, in addition to Golgi fragmentation, increased F-actin content in the absence of FMNL1 also led to cation-independent mannose 6-phosphate receptor dispersal, lysosomal enlargement and missorting of cathepsin D. Taken together, our data support a model in which FMNL1 regulates cellular F-actin levels required to maintain structural integrity of the Golgi complex and lysosomes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55901, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Colón-Franco
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Gomez
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
mesh_terms: D000199:Actins / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton; D000080865:Formins; D006056:Golgi Apparatus / Q000378:metabolism* / Q000473:pathology; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D019169:Jurkat Cells; D008247:Lysosomes / Q000187:drug effects / Q000473:pathology*; D015394:Molecular Structure; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; C476204:FMNL1 protein, human; D000080865:Formins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D002402:Cathepsin D