Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules

Abstract

SummaryThe 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.

MZT1 regulates microtubule nucleation by linking γTuRC assembly to adapter-mediated targeting and activation

“…Pericentrin, AKAP9, CDK5RAP2 and myomegalin have been implicated in γTuRC recruitment to the centrosome (Fong et al, 2008;Takahashi et al, 2002;Zimmerman et al, 2004) and to the Golgi, which functions as a non-centrosomal MTOC (Rivero et al, 2009;Roubin et al, 2013;Wang et al, 2010). All of these proteins contain a CM1 motif (Lin et al, 2014(Lin et al, , 2015Samejima et al, 2008;Sawin et al, 2004), whereas an SPM motif is found only in pericentrin and AKAP9 (Lin et al, 2014(Lin et al, , 2015.…”

Efficacy and Mechanism of a Glycoside Compound Inhibiting Abnormal Prion Protein Formation in Prion-Infected Cells: Implications of Interferon and Phosphodiesterase 4D-Interacting Protein

“…Apparently, Pde4dip functions as an anchor to localize components of the cAMP-dependent pathway to the Golgi apparatus/centrosomal region of the cell. Pde4dip has also been described as a microtubule nucleation activator and is related to regulating microtubule growth (11). Depletion of Pde4dip delays microtubule growth from the centrosome and Golgi apparatus.…”

“…Pde4dip is also called myomegalin and interacts with the cyclic nucleotide phosphodiesterase 4D. It is thought to function as a microtubule nucleation activator (11) and as an anchoring protein that sequesters members of the cyclic AMP (cAMP)-dependent pathway to the Golgi apparatus and to centrosomes (12).…”

Transcriptome Changes Associated with Protective Immunity in T and B Cell-Deficient <i>Rag1<sup>-/-</sup> </i> Mutant Zebrafish

“…Four genes encode over 20 isoforms of this protein, and they are involved in intracellular signaling [57]. Intracellular signaling and cross-talk occurs between cells and between pathways, and between tissues.…”

“…Pathway interactions operate in multiple directions. The cAMP phosphodiesterases are required for cell signaling and crosstalk [57]. Certain isoforms of myomegalin are necessary for centrosomal microtubule formation [58] and protein trafficking between Golgi and endoplasmic reticulum [59].…”