title: Drosophila pod-1 crosslinks both actin and microtubules and controls the targeting of axons.
abstract: Actin and microtubules (MTs) are tightly coordinated during neuronal growth cone navigation and are dynamically regulated in response to guidance cues; however, little is known about the underlying molecular mechanisms. Here, we characterize Drosophila pod-1 (dpod1) and show that purified Dpod1 can crosslink both actin and MTs. In cultured S2 cells, Dpod1 colocalizes with lamellar actin and MTs, and overexpression remodels the cytoskeleton to promote dynamic neurite-like actin-dependent projections. Consistent with these observations, Dpod1 localizes to the tips of growing axons, regions where actin and MTs interact, and is especially abundant at navigational choice points. In either the absence or overabundance of Dpod1, growth cone targeting but not outgrowth is disrupted. Taken together, these results reveal novel activities for pod-1 and show that proper levels of Dpod1, an actin/MT crosslinker, must be maintained in the growth cone for correct axon guidance.
authors.affiliation: Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Rogers
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
authors.forename: Yuh-Nung
authors.initials: YN
authors.lastname: Jan
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D004330:Drosophila; D029721:Drosophila Proteins; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D020439:Growth Cones / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000199:Actins; D029721:Drosophila Proteins; C491826:Pod1 protein, Drosophila; D014157:Transcription Factors