title: Drosophila Ringmaker regulates microtubule stabilization and axonal extension during embryonic development.
abstract: Axonal growth and targeting are fundamental to the organization of the nervous system, and require active engagement of the cytoskeleton. Polymerization and stabilization of axonal microtubules is central to axonal growth and maturation of neuronal connectivity. Studies have suggested that members of the tubulin polymerization promoting protein (TPPP, also known as P25α) family are involved in cellular process extension. However, no in vivo knockout data exists regarding its role in axonal growth during development. Here, we report the characterization of Ringmaker (Ringer; CG45057), the only Drosophila homolog of long p25α proteins. Immunohistochemical analyses indicate that Ringer expression is dynamically regulated in the embryonic central nervous system (CNS). ringer-null mutants show cell misplacement, and errors in axonal extension and targeting. Ultrastructural examination of ringer mutants revealed defective microtubule morphology and organization. Primary neuronal cultures of ringer mutants exhibit defective axonal extension, and Ringer expression in cells induced microtubule stabilization and bundling into rings. In vitro assays showed that Ringer directly affects tubulin, and promotes microtubule bundling and polymerization. Together, our studies uncover an essential function of Ringer in axonal extension and targeting through proper microtubule organization.
authors.affiliation: Department of Physiology, University of Texas School of Medicine, Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Rosa E
authors.initials: RE
authors.lastname: Mino
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Rogers
authors.affiliation: Department of Pharmacology, University of Texas School of Medicine, Health Science Center, San Antonio, TX 78229, USA.
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.affiliation: Department of Pharmacology, University of Texas School of Medicine, Health Science Center, San Antonio, TX 78229, USA Department of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rohena
authors.affiliation: Department of Physiology, University of Texas School of Medicine, Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Physiology, University of Texas School of Medicine, Health Science Center, San Antonio, TX 78229, USA bhatm@uthscsa.edu.
authors.forename: Manzoor A
authors.identifier: 0000-0003-0989-1498
authors.initials: MA
authors.lastname: Bhat
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000378:metabolism; D047108:Embryonic Development; D056426:Genetic Loci; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D058105:Polymerization
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C118136:TPPP protein, human; C000621739:ringer protein, Drosophila
keywords: Axon growth; Cytoskeleton; Microtubules; Nervous system; TPPP; Tubulin polymerization; Tubulin stabilization