Caenorhabditis elegans beta-G spectrin is dispensable for establishment ofepithelial polarity, but essential for muscular and neuronal function

The Caenorhabditis elegans genome encodes one alpha spectrin subunit, a bet a spectrin subunit (beta-G), and a beta-H spectrin subunit. Our experiments show that the phenotype resulting from the loss of the C. elegans alpha sp ectrin is reproduced by tandem depletion of both beta-G and beta-H spectrin s. We propose that alpha spectrin combines with the beta-G and beta-H subun its to form alpha/beta-G and alpha/beta-H heteromers that perform the entir e repertoire of spectrin function in the nematode. The expression patterns of nematode beta-G spectrin and vertebrate beta spectrins exhibit three str iking parallels including: (1) beta spectrins are associated with the sites of cell-cell contact in epithelial tissues; (2) the highest levels of beta -G spectrin occur in the nervous system; and (3) beta spectrin-G in striate d muscle is associated with points of attachment of the myofilament apparat us to adjacent cells. Nematode beta-G spectrin associates with plasma membr anes at sites of cell-cell contact, beginning at the two-cell stage, and wi th a dramatic increase in intensity after gastrulation when most cell proli feration has been completed. Strikingly, depletion of nematode beta-G spect rin by RNA-mediated interference to undetectable levels does not affect the establishment of structural and functional polarity in epidermis and intes tine. Contrary to recent speculation, beta-G spectrin is not associated wit h internal membranes and depletion of beta-G spectrin was not associated wi th any detectable defects in secretion. Instead beta-G spectrin-deficient n ematodes arrest as early larvae with progressive defects in the musculature and nervous system. Therefore, C,elegans beta-G spectrin is required for n ormal muscle and neuron function, but is dispensable for embryonic elongati on and establishment of early epithelial polarity. We hypothesize that hete romeric spectrin evolved in metazoans in response to the needs of cells in the context of mechanically integrated tissues that can withstand the rigor s imposed by an active organism.