QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/dev.00401

This Article Figures Only Full Text 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 Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Osada, S.-I. Articles by Taira, M. Search for Related Content PubMed PubMed Citation Articles by Osada, S.-I. Articles by Taira, M.

XMAN1, an inner nuclear membrane protein, antagonizes BMP signaling by interacting with Smad1 in Xenopus embryos

Department of Biological Sciences, Graduate School of Science, University of Tokyo, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan

^* Author for correspondence (e-mail: m_taira{at}biol.s.u-tokyo.ac.jp)

Accepted 16 January 2003

A family of inner nuclear membrane proteins is implicated in gene regulation by interacting with chromatin, nuclear lamina and intranuclear proteins; however, the physiological functions of these proteins are largely unknown. Using a Xenopus expression screening approach with an anterior neuroectoderm cDNA library, we have identified an inner nuclear membrane protein, XMAN1, as a novel neuralizing factor that is encoded by the Xenopus ortholog of human MAN1. XMAN1 mRNA is expressed maternally, and appears to be restricted to the entire ectoderm at the early gastrula stage, then to the anterior neuroectoderm at the neurula stage. XMAN1 induces anterior neural markers without mesoderm induction in ectodermal explants, and a partial secondary axis when expressed ventrally by dorsalizing the ventral mesoderm. Importantly, XMAN1 antagonizes bone morphogenetic protein (BMP) signaling downstream of its receptor Alk3, as judged by animal cap assays, in which XMAN1 blocks expression of downstream targets of BMP signaling (Xhox3 and Msx1), and by luciferase reporter assays, in which XMAN1 suppresses BMP-dependent activation of the Xvent2 promoter. Deletion mutant analyses reveal that the neuralizing and BMP-antagonizing activities of XMAN1 reside in the C-terminal region, and that the C-terminal region binds to Smad1, Smad5 and Smad8, which are intracellular mediators of the BMP pathway. Interference with endogenous XMAN1 functions with antisense morpholino oligos leads to the reduction of anterior neuroectoderm. These results provide the first evidence that the nuclear envelope protein XMAN1 acts as a Smad-interacting protein to antagonize BMP signaling during Xenopus embryogenesis.

Key words: Xenopus laevis, Neuralization, BMP signaling, Smad, Inner nuclear membrane protein, MAN1

Related articles in Development:

Novel antagonist of BMP signalling

Development 2003 130: 901. [Full Text]  

This article has been cited by other articles:

				B. S. Pinto, S. R. Wilmington, E. E. L. Hornick, L. L. Wallrath, and P. K. Geyer Tissue-Specific Defects Are Caused by Loss of the Drosophila MAN1 LEM Domain Protein Genetics, September 1, 2008; 180(1): 133 - 145. [Abstract] [Full Text] [PDF]

				Y. Tsuchiya Till Disassembly Do Us Part: A Happy Marriage of Nuclear Envelope and Chromatin J. Biochem., February 1, 2008; 143(2): 155 - 161. [Abstract] [Full Text] [PDF]

				C. L. Stewart, K. J. Roux, and B. Burke Blurring the Boundary: The Nuclear Envelope Extends Its Reach Science, November 30, 2007; 318(5855): 1408 - 1412. [Abstract] [Full Text] [PDF]

				T. V. Cohen, O. Kosti, and C. L. Stewart The nuclear envelope protein MAN1 regulates TGF{beta} signaling and vasculogenesis in the embryonic yolk sac Development, April 1, 2007; 134(7): 1385 - 1395. [Abstract] [Full Text] [PDF]

				A. Zargari, M. Boban, S. Heessen, C. Andreasson, J. Thyberg, and P. O. Ljungdahl Inner Nuclear Membrane Proteins Asi1, Asi2, and Asi3 Function in Concert to Maintain the Latent Properties of Transcription Factors Stp1 and Stp2 J. Biol. Chem., January 5, 2007; 282(1): 594 - 605. [Abstract] [Full Text] [PDF]

				J. M. Holaska, S. Rais-Bahrami, and K. L. Wilson Lmo7 is an emerin-binding protein that regulates the transcription of emerin and many other muscle-relevant genes Hum. Mol. Genet., December 1, 2006; 15(23): 3459 - 3472. [Abstract] [Full Text] [PDF]

				A. Ishimura, J. K. Ng, M. Taira, S. G. Young, and S.-I. Osada Man1, an inner nuclear membrane protein, regulates vascular remodeling by modulating transforming growth factor {beta} signaling Development, October 1, 2006; 133(19): 3919 - 3928. [Abstract] [Full Text] [PDF]

				J. L. V. Broers, F. C. S. Ramaekers, G. Bonne, R. B. Yaou, and C. J. Hutchison Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev, July 1, 2006; 86(3): 967 - 1008. [Abstract] [Full Text] [PDF]

				S. Caputo, J. Couprie, I. Duband-Goulet, E. Konde, F. Lin, S. Braud, M. Gondry, B. Gilquin, H. J. Worman, and S. Zinn-Justin The Carboxyl-terminal Nucleoplasmic Region of MAN1 Exhibits a DNA Binding Winged Helix Domain J. Biol. Chem., June 30, 2006; 281(26): 18208 - 18215. [Abstract] [Full Text] [PDF]

				M. Boban, A. Zargari, C. Andreasson, S. Heessen, J. Thyberg, and P. O. Ljungdahl Asi1 is an inner nuclear membrane protein that restricts promoter access of two latent transcription factors J. Cell Biol., June 5, 2006; 173(5): 695 - 707. [Abstract] [Full Text] [PDF]

				A. Brachner, S. Reipert, R. Foisner, and J. Gotzmann LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins J. Cell Sci., December 15, 2005; 118(24): 5797 - 5810. [Abstract] [Full Text] [PDF]

				D. Pan, L. D. Estevez-Salmeron, S. L. Stroschein, X. Zhu, J. He, S. Zhou, and K. Luo The Integral Inner Nuclear Membrane Protein MAN1 Physically Interacts with the R-Smad Proteins to Repress Signaling by the Transforming Growth Factor-{beta} Superfamily of Cytokines J. Biol. Chem., April 22, 2005; 280(16): 15992 - 16001. [Abstract] [Full Text] [PDF]

				M. Mansharamani and K. L. Wilson Direct Binding of Nuclear Membrane Protein MAN1 to Emerin in Vitro and Two Modes of Binding to Barrier-to-Autointegration Factor J. Biol. Chem., April 8, 2005; 280(14): 13863 - 13870. [Abstract] [Full Text] [PDF]

				F. Lin, J. M. Morrison, W. Wu, and H. J. Worman MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-{beta} signaling Hum. Mol. Genet., February 1, 2005; 14(3): 437 - 445. [Abstract] [Full Text] [PDF]

				T. Mochizuki, H. Miyazaki, T. Hara, T. Furuya, T. Imamura, T. Watabe, and K. Miyazono Roles for the MH2 Domain of Smad7 in the Specific Inhibition of Transforming Growth Factor-{beta} Superfamily Signaling J. Biol. Chem., July 23, 2004; 279(30): 31568 - 31574. [Abstract] [Full Text] [PDF]

				C. L. Kielkopf, S. Lucke, and M. R. Green U2AF homology motifs: protein recognition in the RRM world Genes & Dev., July 1, 2004; 18(13): 1513 - 1526. [Abstract] [Full Text] [PDF]

				M. S. Zastrow, S. Vlcek, and K. L. Wilson Proteins that bind A-type lamins: integrating isolated clues J. Cell Sci., March 1, 2004; 117(7): 979 - 987. [Abstract] [Full Text] [PDF]

				I. Hiratani, N. Yamamoto, T. Mochizuki, S.-y. Ohmori, and M. Taira Selective degradation of excess Ldb1 by Rnf12/RLIM confers proper Ldb1 expression levels and Xlim-1/Ldb1 stoichiometry in Xenopus organizer functions Development, September 1, 2003; 130(17): 4161 - 4175. [Abstract] [Full Text] [PDF]