A model for sealing plasmalemmal damage in neurons and other eukaryotic cells

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dc.contributor.utaustinauthorSpaeth, Christopher S.
dc.contributor.utaustinauthorBoydston, Elaine A.
dc.contributor.utaustinauthorFigard, Lauren R.
dc.contributor.utaustinauthorZuzek, Aleksej
dc.contributor.utaustinauthorBittner, George D.
dc.creatorSpaeth, Christopher S.
dc.creatorBoydston, Elaine A.
dc.creatorFigard, Lauren R.
dc.creatorZuzek, Aleksej
dc.creatorBittner, George D.
dc.date.accessioned2016-05-31T20:14:04Z
dc.date.available2016-05-31T20:14:04Z
dc.date.issued2010-11-24en
dc.description.abstractPlasmalemmal repair is necessary for survival of damaged eukaryotic cells. Ca2 influx through plasmalemmal disruptions activates calpain, vesicle accumulation at lesion sites, and membrane fusion proteins; Ca2 influx also initiates competing apoptotic pathways. Using the formation of a dye barrier (seal) to assess plasmalemmal repair, we now report that B104 hippocampal cells with neurites transected nearer ( 50 m)to the soma seal at a lower frequency and slower rate compared to cells with neurites transected farther ( 50 m) from the soma. Analogs of cAMP, including protein kinase A (PKA)-specific and Epac-specific cAMP, each increase the frequency and rate of sealing and can even initiate sealing in the absence of Ca2 influx at both transection distances. Furthermore, Epac activates a cAMP-dependent, PKA-independent, pathway involved in plasmalemmal sealing. The frequency and rate of plasmalemmal sealing are decreased by a small molecule inhibitor of PKA targeted to its catalytic subunit (KT5720), a peptide inhibitor targeted to its regulatory subunits (PKI), an inhibitor of a novel PKC (an nPKC pseudosubstrate fragment), and an antioxidant (melatonin). Given these and other data, we propose a model for redundant parallel pathways of Ca2 -dependent plasmalemmal sealing of injured neurons mediated in part by nPKCs, cytosolic oxidation, and cAMP activation of PKA and Epac. We also propose that the evolutionary origin of these pathways and substances was to repair plasmalemmal damage in eukaryotic cells. Greater understanding of vesicle interactions, proteins, and pathways involved in plasmalemmal sealing should suggest novel neuroprotective treatments for traumatic nerve injuries and neurodegenerative disorders.en_US
dc.description.departmentNeuroscienceen_US
dc.description.sponsorshipThis work was funded by grants from the Lone Star Paralysis Foundation.en_US
dc.identifierdoi:10.15781/T2QZ22H0J
dc.identifier.citationC.S. Spaeth, E.A. Boydston, L.A. Figard, A. Zuzek and G.D. Bittner. 2010. A model for sealing plasmalemmal damage in neurons and other eukaryotic cells. J. Neurosci. 30:15790-15800. doi: 10.1523/JNEUROSCI.4155-10.2010. PubMed PMID: 21106818.en_US
dc.identifier.doi10.1523/JNEUROSCI.4155-10.2010
dc.identifier.urihttp://hdl.handle.net/2152/37806
dc.language.isoengen_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.ispartofUT Faculty/Researcher Worksen_US
dc.rights.restrictionOpenen_US
dc.subjectplasmalemmal repairen_US
dc.titleA model for sealing plasmalemmal damage in neurons and other eukaryotic cellsen_US
dc.typeArticleen_US

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