The Lnx family proteins function as molecular scaffolds for Numb family proteins

Drosophila Numb functions as a cell fate determinant during neurogenesis. We isolated a novel mammalian protein, Lnx2, which interacts with mammalian Numb and Numblike. Lnx2 and the related Lnx1 are multimodular proteins that bind to Numb via their NPXY motifs. In addition, Lnx proteins form oligomers either via their PDZ domains binding to PDZ-binding consensus motifs located in their C-termini or by homophilic oligomerization of their RING fingers. Therefore, Lnx proteins may form large networks by homomeric binding. In situ hybridization analysis revealed complementary patterns of Lnx1 and Lnx2 expression in developing and adult brain, although in several structures they are present in the same cell populations. Moreover, their expression patterns overlap with those of the Numb proteins. Oligomerization of Lnx2 and Numb binding occurs simultaneously. Therefore, our findings suggest that Lnx proteins may serve as molecular scaffolds that localize unrelated, interacting proteins, such as Numb, to specific subcellular sites.