A cell's interactions with other cells and ability to adapt to its environment are dependent on proteins associated on its plasma membrane. Ankyrin, an intracellular protein that couples several integral membrane proteins to the spectrin cytoskeleton, is instrumental in organizing many membrane proteins into specialized domains. Recently, the L1 family of neuronal cell adhesion molecules, was shown to bind ankyrin. These proteins, which include L1, NrCAM, Ng CAM, neurofascin, and CHL1, are believed to be involved in neurite outgrowth and axonal fasciculation and targeting during development. In Drosophila, a single L1 family homologue, neuroglian, was identified and characterized. Loss of function mutations in neuroglian result in animals that arrest as larvae. Interestingly, there is no obvious defect in the development of their nervous system. A homologue of the family has been identified in C. elegans (Yuji Kohara and genome sequencing), and has been designated
lad-1 ( L 1-like AD hesion).
lad-1 is closely linked to
unc-24 on chromosome IV. As with the L1 family members, LAD-1 possesses variable extracellular domains composed of six Ig and five FNIII domains, a transmembrane domain, and a cytoplasmic tail that contains a highly conserved ankyrin-binding domain. We are interested in determining LAD-1's function and studying its interaction with UNC-44, the C. elegans ankyrin homologue. As a first step, we compared LAD-1 expression with that of UNC-44.
lad-1 is expressed in the nervous system, with the nerve ring, and the ventral and dorsal nerve cords showing robust staining.
lad-1 is also expressed in body wall muscles, hypodermal cells, and the gonad. While LAD-1 and UNC-44 appear to colocalize in the same tissues, we will further test their interaction using biochemical means. We used both RNAi and dominant negative constructs to interfere with endogenous LAD-1 function. Both approaches resulted in animals that were Vab and Unc, with variable lethality. Apparently,
lad-1 function is required for viability and proper morphogenesis. Screens for a genetic
lad-1 mutant are currently being carried out, which will be important in determining the role of
lad-1 .