Mutations in β-spectrin disrupt axon outgrowth and sarcomere structure

Abstract

β-Spectrin is a major component of the membrane skeleton, a structure found at the plasma membrane of most animal cells. β-Spectrin and the membrane skeleton have been proposed to stabilize cell membranes, generate cell polarity, or localize specific membrane proteins. We demonstrate that the Caenorhabditis elegans homologue of β-spectrin is encoded by the unc-70 gene. unc-70 null mutants develop slowly, and the adults are paralyzed and dumpy. However, the membrane integrity is not impaired in unc-70 animals, nor is cell polarity affected. Thus, β-spectrin is not essential for general membrane integrity or for cell polarity. However, β-spectrin is required for a subset of processes at cell membranes. In neurons, the loss of β-spectrin leads to abnormal axon outgrowth. In muscles, a loss of β-spectrin leads to disorganization of the myofilament lattice, discontinuities in the dense bodies, and a reduction or loss of the sarcoplasmic reticulum. These defects are consistent with β-spectrin function in anchoring proteins at cell membranes.