Originally published as Genetics Published Articles Ahead of Print on September 14, 2008.

Genetics, Vol. 180, 1429-1443, November 2008, Copyright © 2008
doi:10.1534/genetics.108.091272

unc-44 Ankyrin and stn-2 {gamma}-Syntrophin Regulate sax-7 L1CAM Function in Maintaining Neuronal Positioning in Caenorhabditis elegans

Shan Zhou1, Karla Opperman1, Xuelin Wang and Lihsia Chen2

Department of Genetics, Cell Biology and Development, Developmental Biology Center, University of Minnesota, Minneapolis, Minnesota 55455

2 Corresponding author: University of Minnesota, 6-160 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455. 
E-mail: chenx260{at}umn.edu

The L1 family of single-pass transmembrane cell adhesion molecules (L1CAMs) is conserved from Caenorhabditis elegans and Drosophila to vertebrates and is required for axon guidance, neurite outgrowth, and maintenance of neuronal positions. The extracellular region of L1CAMs mediates cell adhesion via interactions with diverse cell-surface and extracellular matrix proteins. In contrast, less is known regarding the function of the intracellular domains in the L1CAM cytoplasmic tail. Previously, we identified a role of the C. elegans L1CAM homolog, SAX-7, in maintaining neuronal and axonal positioning. Here, we demonstrate that this function is dependent on three conserved motifs that reside in the SAX-7 cytoplasmic tail: (1) the FERM-binding motif, (2) the ankyrin-binding domain, and (3) the PDZ-binding motif. Furthermore, we provide molecular and genetic evidence that UNC-44 ankyrin and STN-2 {gamma}-syntrophin bind SAX-7 via the respective ankyrin-binding and PDZ-binding motifs to regulate SAX-7 function in maintaining neuronal positioning.