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First published online 14 April 2008
doi: 10.1242/jcs.017137

Journal of Cell Science 121, 1477-1487 (2008)
Published by The Company of Biologists 2008
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Research Article

Dynamic analysis identifies novel roles for DLG-1 subdomains in AJM-1 recruitment and LET-413-dependent apical focusing

Christopher A. Lockwood1, Allison M. Lynch1 and Jeff Hardin1,2,*

1 Program in Genetics, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA
2 Department of Zoology, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA

* Author for correspondence (e-mail: jdhardin{at}wisc.edu)

Accepted 7 February 2008

Cell-cell junctions are composed of a diverse array of specialized proteins that are necessary for the movement and integrity of epithelia. Scaffolding molecules, such as membrane-associated guanylate kinases (MAGUKs) contain multiple protein-protein interaction domains that integrate these proteins into macromolecular complexes at junctions. We have used structure-function experiments to dissect the role of domains of the Caenorhabditis elegans MAGUK DLG-1, a homolog of Drosophila Discs large and vertebrate SAP97. DLG-1 deletion constructs were analyzed in directed yeast two-hybrid tests as well as in vivo in a dlg-1 null mutant background. Our studies identify novel roles for several key domains. First, the L27 domain of DLG-1 mediates the physical interaction of DLG-1 with its binding partner, AJM-1, as well as DLG-1 multimerization. Second, the PDZ domains of DLG-1 mediate its association with the junction. Third, using dynamic in vivo imaging, we demonstrate that the SH3 domain is required for rapid lateral distribution of DLG-1 via a LET-413/Scribble-dependent pathway. Finally, we found that inclusion of the SH3 domain can ameliorate dlg-1 mutant phenotypes, but full rescue of lethality required the complete C terminus, which includes the GUK and Hook domains, thereby demonstrating the importance of the C-terminus for DLG-1 function. Our results represent the first in vivo analysis of requirements for the L27 domain of a Discs-large/SAP97 protein, identify a crucial LET-413/Scribble regulatory motif and provide insight into how MAGUK subdomains function to maintain epithelial integrity during development.

Key words: Cell-cell junction, MAGUK, Discs large, Morphogenesis






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