SEQUENTIAL EVENTS IN NEURITE OUTGROWTH AND STABILIZATION

点击翻译按钮获取中文摘要

Following synaptogenesis, the extensively cross-linked infrastructure of an axon may remain basically unaltered throughout the lifetime of the neuron; accordingly, the stabilization of the axonal cytoskeleton may be a key event in the establishment of mature neuronal morphology, and, in turn, the orderly development of the nervous system and maintenance of its functionality. However, it remains unclear how a neuron initiates neurite outgrowth, and subsequently effects the orderly transition of its axonal cytoskeleton from the presumably flexible structure of a rapidly- growing neurite to the stabilized latticework characteristic of mature axons. During embryonic brain development, there is a window of time in which the postmigratory neuoblast contains sufficient pools of protein constituents necessary for neuritogenesis. The initial events, which occur independently of protein synthesis encompass the translocation of previously established pools of membrane-associated, membrane-skeletal, and cytoskeletal proteins into the newly-elaborated neurite. These epignetic events are followed by the establishment of a mature axonal cytoskeleton -- a process which is dependent upon synthesis and posttranslational modification of additional protein species. Our results further indicate that certain protein constituents are specifically involved in the elaboration of neurites, and are subsequently replaced by others (or, in some cases, isoforms whose properties have been drastically altered by late-appearing posttranslational modifications) which mediate stabilization of the axonal cytoskeletal lattice. The proposed experiments are designed to elucidate (1) which of the relevent proteins are present in undifferentiated cells in sufficient quantities to support neuritogenesis in the absence of aditional synthesis, and in what order they are translocated into the axon; (2) which species or isoforms appear only following differentiation-related alterations in genetic expressiom; and, finally, (3) which constituents confer stability to the cytoskeletal lattice and at what stage they appear.