A novel myomegalin isoform functions in Golgi microtubule organization and ER-Golgi transport

Abstract

The Golgi apparatus of mammalian cells is known to be a major microtubule-organizing site that requires microtubules for its organization and protein trafficking. However, the mechanisms underlying the microtubule organization of the Golgi apparatus remain obscure. We used immunoprecipitation coupled with mass spectrometry to identify a widely expressed isoform of the poorly characterized muscle protein myomegalin. This novel isoform, myomegalin variant 8 (MMG8), localized predominantly to cis-Golgi networks by interacting with AKAP450, and this interaction with AKAP450 was required for the stability of both proteins. Disrupting MMG8 expression affected ER-to-Golgi trafficking and caused Golgi fragmentation. Furthermore, MMG8 associated with γ-tubulin complexes and with the microtubule plus-end tracking protein EB1, and MMG8 was required for the Golgi localization of these 2 molecules. On the Golgi, γ-tubulin complexes mediated microtubule nucleation, whereas EB1 functioned in ER-to-Golgi trafficking. These results indicate that MMG8 participates in Golgi microtubule organization and thereby plays a crucial role in the organization and function of the Golgi apparatus.