title: Drosophila Spire is an actin nucleation factor.
abstract: The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor. In vitro, Spire nucleates new filaments at a rate that is similar to that of the formin family of proteins but slower than in the activated Arp2/3 complex, and it remains associated with the slow-growing pointed end of the new filament. Spire contains a cluster of four WASP homology 2 (WH2) domains, each of which binds an actin monomer. Maximal nucleation activity requires all four WH2 domains along with an additional actin-binding motif, conserved among Spire proteins. Spire itself is conserved among metazoans and, together with the formin Cappuccino, is required for axis specification in oocytes and embryos, suggesting that multiple actin nucleation factors collaborate to construct essential cytoskeletal structures.
authors.affiliation: Department of Cellular and Molecular Pharmacology, UCSF Medical School, San Francisco, California 94107, USA.
authors.forename: Margot E
authors.initials: ME
authors.lastname: Quinlan
authors.forename: John E
authors.initials: JE
authors.lastname: Heuser
authors.forename: Eugen
authors.initials: E
authors.lastname: Kerkhoff
authors.forename: R Dyche
authors.initials: RD
authors.lastname: Mullins
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism*; D000199:Actins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; C402385:spir protein, Drosophila