title: Parallel genetic and proteomic screens identify Msps as a CLASP-Abl pathway interactor in Drosophila.
abstract: Regulation of cytoskeletal structure and dynamics is essential for multiple aspects of cellular behavior, yet there is much to learn about the molecular machinery underlying the coordination between the cytoskeleton and its effector systems. One group of proteins that regulate microtubule behavior and its interaction with other cellular components, such as actin-regulatory proteins and transport machinery, is the plus-end tracking proteins (MT+TIPs). In particular, evidence suggests that the MT+TIP, CLASP, may play a pivotal role in the coordination of microtubules with other cellular structures in multiple contexts, although the molecular mechanism by which it functions is still largely unknown. To gain deeper insight into the functional partners of CLASP, we conducted parallel genetic and proteome-wide screens for CLASP interactors in Drosophila melanogaster. We identified 36 genetic modifiers and 179 candidate physical interactors, including 13 that were identified in both data sets. Grouping interactors according to functional classifications revealed several categories, including cytoskeletal components, signaling proteins, and translation/RNA regulators. We focused our initial investigation on the MT+TIP Minispindles (Msps), identified among the cytoskeletal effectors in both genetic and proteomic screens. Here, we report that Msps is a strong modifier of CLASP and Abl in the retina. Moreover, we show that Msps functions during axon guidance and antagonizes both CLASP and Abl activity. Our data suggest a model in which CLASP and Msps converge in an antagonistic balance in the Abl signaling pathway.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Lowery
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Murphy
authors.forename: R A
authors.initials: RA
authors.lastname: Obar
authors.forename: B
authors.initials: B
authors.lastname: Zhai
authors.forename: M
authors.initials: M
authors.lastname: Schedl
authors.forename: D
authors.initials: D
authors.lastname: Van Vactor
authors.forename: Y
authors.initials: Y
authors.lastname: Zhan
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012160:Retina / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C407307:chb protein, Drosophila; C121511:msps protein, Drosophila; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila