α-Actinins, Calspectin (Brain Spectrin or Fodrin), and Actin Participate in Adhesion and Movement of Growth Cones

Abstract We have used biochemical and immunocytochemical techniques to investigate the possible involvement of membrane cytoskeletal elements such as α-actinin, calspectin (brain spectrin or fodrin), and actin in growth cone activities. During NGF-induced differentiation of PC12 cells, α-actinin increased in association with neurite outgrowth and was predominantly distributed throughout the entire growth cone and the distal portion of neurites. Filopodial movements were sensitive to Ca 2+ flux. Two types of α-actinin, with Ca 2+ sensitive and -insensitive actin binding abilities, were identified in the differentiated cells. Ca 2+ -sensitive α-actinin and actin filaments were concentrated in filopodia. The Ca 2+ -insensitive protein was distributed from the body of the growth cone to the distal portion of neurites, corresponding to the substratum-adhesive sites. The location of calspectin in growth cones was similar to that of the Ca 2+ -insensitive α-actinin. These results are consistent with the hypothesis that Ca 2+ sensitive α-actinin and actin filaments are involved in Ca 2+ -dependent filopodial movement and Ca 2+ -insensitive α-actinin and calspectin are associated with adhesion of growth cones.