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unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration

Daniel A. Starr¹, Greg J. Hermann², Christian J. Malone^1,*, William Fixsen^3,, James R. Priess², H. Robert Horvitz³ and Min Han^1,

¹ Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
² Howard Hughes Medical Institute and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
³ Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
^* Present address: Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA
Present address: Department of Continuing Education, Harvard University, Cambridge, MA 02138, USA

Author for correspondence (e-mail: mhan{at}colorado.edu)

Accepted September 20, 2001

Nuclear migration plays an essential role in the growth and development of a wide variety of eukaryotes. Mutations in unc-84, which encodes a conserved component of the nuclear envelope, have been shown to disrupt nuclear migration in two C. elegans tissues. We show that mutations in unc-83 disrupt nuclear migration in a similar manner in migrating P cells, hyp7 precursors and the intestinal primordium, but have no obvious defects in the association of centrosomes with nuclei or the structure of the nuclear lamina of migrating nuclei. We also show that unc-83 encodes a novel transmembrane protein. We identified three unc-83 transcripts that are expressed in a tissue-specific manner. Antibodies against UNC-83 co-localized to the nuclear envelope with lamin and UNC-84. Unlike UNC-84, UNC-83 localized to only specific nuclei, many of which were migratory. UNC-83 failed to localize to the nuclear envelope in unc-84 mutants with lesions in the conserved SUN domain of UNC-84, and UNC-83 interacted with the SUN domain of UNC-84 in vitro, suggesting that these two proteins function together during nuclear migration. We favor a model in which UNC-84 directly recruits UNC-83 to the nuclear envelope where they help transfer force between the cytoskeleton and the nucleus.

Key words: UNC-83, UNC-84, Nuclear envelope, Nuclear migration, C. elegans

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