title: Formin-mediated actin polymerization cooperates with Mushroom body defect (Mud)-Dynein during Frizzled-Dishevelled spindle orientation.
abstract: To position the mitotic spindle, cytoskeletal components must be coordinated to generate cortical forces on astral microtubules. Although the dynein motor is common to many spindle orientation systems, 'accessory pathways' are often also required. In this work, we identified an accessory spindle orientation pathway in Drosophila that functions with Dynein during planar cell polarity, downstream of the Frizzled (Fz) effector Dishevelled (Dsh). Dsh contains a PDZ ligand and a Dynein-recruiting DEP domain that are both required for spindle orientation. The Dsh PDZ ligand recruits Canoe/Afadin and ultimately leads to Rho GTPase signaling mediated through RhoGEF2. The formin Diaphanous (Dia) functions as the Rho effector in this pathway, inducing F-actin enrichment at sites of cortical Dsh. Chimeric protein experiments show that the Dia-actin accessory pathway can be replaced by an independent kinesin (Khc73) accessory pathway for Dsh-mediated spindle orientation. Our results define two 'modular' spindle orientation pathways and show an essential role for actin regulation in Dsh-mediated spindle orientation.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Johnston
authors.forename: Laurina
authors.initials: L
authors.lastname: Manning
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Lu
authors.forename: Ognjen
authors.initials: O
authors.lastname: Golub
authors.forename: Chris Q
authors.initials: CQ
authors.lastname: Doe
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Prehoda
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D058105:Polymerization; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008840:Microfilament Proteins; D010750:Phosphoproteins; C000606588:dsh protein, Drosophila; D004398:Dyneins
keywords: Drosophila melanogaster; Dynein; Formins; Small GTPases; Spindle orientation