title: The actin-microtubule cross-linking activity of Drosophila Short stop is regulated by intramolecular inhibition.
abstract: Actin and microtubule dynamics must be precisely coordinated during cell migration, mitosis, and morphogenesis--much of this coordination is mediated by proteins that physically bridge the two cytoskeletal networks. We have investigated the regulation of the Drosophila actin-microtubule cross-linker Short stop (Shot), a member of the spectraplakin family. Our data suggest that Shot's cytoskeletal cross-linking activity is regulated by an intramolecular inhibitory mechanism. In its inactive conformation, Shot adopts a "closed" conformation through interactions between its NH(2)-terminal actin-binding domain and COOH-terminal EF-hand-GAS2 domain. This inactive conformation is targeted to the growing microtubule plus end by EB1. On activation, Shot binds along the microtubule through its COOH-terminal GAS2 domain and binds to actin with its NH(2)-terminal tandem CH domains. We propose that this mechanism allows Shot to rapidly cross-link dynamic microtubules in response to localized activating signals at the cell cortex.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280 Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Applewhite
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Grode
authors.forename: Mara C
authors.initials: MC
authors.lastname: Duncan
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Rogers
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D003432:Cross-Linking Reagents / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D020832:EF Hand Motifs; D005453:Fluorescence; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D000199:Actins; D003432:Cross-Linking Reagents; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C450828:shot protein, Drosophila