Axonal growth and maintenance depend on the delivery of new membrane material to neuronal processes. New membrane is synthesized in the cell bodies of neurons, transported down the axon along microtubules, and inserted into the plasmalemma. The cellular mechanisms which determine the topology of new membrane addition to the growing nerve processes remain unknown. Our recent data suggest that the pattern of new membrane insertion into nerve processes may be regulated by assembly/disassembly of axonal microtubles. To test this hypothesis, the following specific aims will be addressed: 1) To investigate regulation of membrane traffic by assembly/disassembly of axonal microtubules; 2) To examine regulation of new membrane insertion into the plasmalemma by intracellular messengers and extracellular stimuli; 3) To investigate regulation of vesicular transport and new membrane insertion into the plasmalemma by microtubule-associated protein tau and by Op18/stathmin. We will use a combination of digital fluorescence microscopy and molecular biology techniques to address these specific aims. The proposed studies will provide new information concerning the mechanisms of nerve growth and development. The results of this work are critical for the rational design of new therapeutic strategies aimed at the treatment of developmental disorders of the central nervous system and trauma such as stroke and spinal cord injury.
