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First published online September 12, 2006

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MAN1y interactions shape vascular development

Although the function of some inner nuclear membrane proteins is known, the function of others - including Man1 - remains unclear. Man1 negatively regulates Tgfß signalling by interacting with receptor-associated Smads in cultured cells. But what is its role in vivo? On p. 3919, Ishimura and colleagues propose that Man1 regulates angiogenesis during mouse embryogenesis by interacting with Smads. Their findings show that embryos in which the Smad-interaction domain of Man1 is deleted die at midgestation, owing to defects in their embryonic vasculature. They report that increased Smad2/3 signalling and Tgfß1 expression in these Man1-deficient embryos cause increased extracellular matrix (ECM) deposition, as is also seen in people with MAN1 mutations. This increased ECM deposition probably inhibits endothelial cell proliferation and migration; the recruitment of smooth muscle cells to the vascular wall is also disturbed. Together, these results suggest that Man1 regulates embryonic vascular remodelling by interacting with receptor-associated Smads at the inner nuclear membrane to ultimately modulate Tgfß signalling.

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Related articles in Development:

Man1, an inner nuclear membrane protein, regulates vascular remodeling by modulating transforming growth factor ß signaling

Akihiko Ishimura, Jennifer K. Ng, Masanori Taira, Stephen G. Young, and Shin-Ichi Osada
Development 2006 133: 3919-3928. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?