title: Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules.
abstract: The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. The microtubule growing plus-ends are stabilized by plus-end tracking proteins (+TIPs), mainly EB1 and associated proteins. Myomegalin was identified as a centrosome/Golgi protein associated with cyclic nucleotide phosphodiesterase. We show here that Myomegalin exists as several isoforms. We characterize two of them. One isoform, CM-MMG, harbors a conserved domain (CM1), recently described as a nucleation activator, and is related to a family of γ-tubulin binding proteins, which includes Drosophila centrosomin. It localizes at the centrosome and at the cis-Golgi in an AKAP450-dependent manner. It recruits γ-tubulin nucleating complexes and promotes microtubule nucleation. The second isoform, EB-MMG, is devoid of CM1 domain and has a unique N-terminus with potential EB1-binding sites. It localizes at the cis-Golgi and can localize to microtubule plus-ends. EB-MMG binds EB1 and affects its loading on microtubules and microtubule growth. Depletion of Myomegalin by small interfering RNA delays microtubule growth from the centrosome and Golgi apparatus, and decreases directional migration of RPE1 cells. In conclusion, the Myomegalin gene encodes different isoforms that regulate microtubules. At least two of these have different roles, demonstrating a previously unknown mechanism to control microtubules in vertebrate cells.
authors: Centre de Recherche en Cancérologie de Marseille ,  INSERM UMR1068, F-13009 Marseille ,  France ; Institut Paoli-Calmettes ,  F-13009 Marseille ,  France ; CNRS U7258, F-13009 Marseille ,  France ; Aix-Marseille Université ,  F-13007 Marseille ,  France.
authors: Régine
authors: R
authors: Roubin
authors: Claire
authors: C
authors: Acquaviva
authors: Véronique
authors: V
authors: Chevrier
authors: Fatima
authors: F
authors: Sedjaï
authors: Déborah
authors: D
authors: Zyss
authors: Daniel
authors: D
authors: Birnbaum
authors: Olivier
authors: O
authors: Rosnet
keywords: Centrosome; EB1; Golgi; Microtubule; γ-Tubulin