Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex

Publication date: 5 June 2017
Source:Developmental Cell, Volume 41, Issue 5
Author(s): Marcela Raices, Lucas Bukata, Stephen Sakuma, Joana Borlido, Leanora S. Hernandez, Daniel O. Hart, Maximiliano A. D'Angelo
Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.

Graphical abstract

Teaser

Nup210 is a tissue-specific nuclear pore complex component with a role in myogenic differentiation. Raices, Bukata et al. show in zebrafish and mammalian myoblasts that Nup210 regulates myofiber maturation, growth, and survival by promoting assembly of a Mef2C-dependent transcription complex at nuclear pores to regulate muscle structural and miRNA genes.


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