References:
- Yoo, S.; Bottenstein, J.E.; Bittner, G.D.; Fishman, H.M. Survival of mammalian B104 cells following neurite transection at different locations depends on somal Ca2+ concentration. J. Neurobiol., in press, 2004.
- Bittner, G.D.; Fishman, H.M. Vesicle-mediated restoration of a plasmalemmal barrier after axonal injury. NIPS, 18:115-118, 2003.
- Yoo, S.; Nguyen, M.P.; Fukuda, M.; Bittner, G.D.; Fishman, H.M. Plasmalemmal sealing of transected mammalian neurites is a gradual process mediated by Ca2+-regulated proteins. J Neurosci Res, 74:541-551, 2003.
Harvey Fishman, SB, MS, PhD
Visiting Professor
UTHSC, Medical School, (713) 500 - 6327
Harvey.M.Fishman@uth.tmc.edu
Fundamental cellular/molecular mechanisms that repair axolemmal damage
We study fundamental cellular/molecular mechanisms that repair axolemmal damage or lead to axonal degeneration. Previously, we described several cellular processes (formation, movement, accumulation, and interactions of Ca2+-induced endocytotic vesicles) that we showed are necessary for successful repair (sealing) of axolemmal lesions (transections and punctures) to prevent degeneration of invertebrate giant axons (GAs) and cultured mammalian neurons after neurite severance. Our present objectives are: 1) To obtain cellular and molecular details of processes by which increased axoplasmic [Ca2+] enables vesicles to seal a damaged axolemmal membrane in our invertebrate GA preparations (squid, crayfish and earthworm) whose large size enables us to obtain detailed data more easily from fluorescently-labeled probes (antibodies to membrane proteins and endogenous and/or exogenous vesicles), time-lapse confocal imaging, fluorescence resonance energy transfer, and electron microscopy. Application of these techniques to these myelinated (earthworm) and unmyelinated (crayfish, squid) invertebrate GA preparations enables us to identify proteins that are essential for successful axolemmal repair and to discriminate between several proposed models of vesicle-mediated sealing. 2) To determine whether the principles and cellular/molecular mechanisms that repair unmyelinated or myelinated invertebrate GAs are conserved in the repair of injured neurites of mammalian neurons in cultures of unmyelinated rat PNS pheochromocytoma (PC12) , rat CNS (B104) cells, and in unmyelinated vs myelinated rat embryonic forebrain cultures at the same stage of development.
