Abstract

The question of how cells form long asymmetric processes will be investigated in Astrocytes and in Sf9 cells infected with baculovirus carrying cDNAs encoding various cytoskeletal proteins. The experiments will look at the role of the myosin light chain, myosin light chain kinase, destrin and protein phosphatases in mediation of astrocytic relaxation and stellation. The role of the actin-rich distal tip of the process in regulation of microtubule assembly in the process shaft will be examined by video microscopy and the microinjection of labeled tubulin and actin. It is proposed that nitric oxide may be an important messenger in the neuronal-induced stellation of astrocytes and in the autoregulation of astrocytic shape which may occur in injury. The necessity for GFAP in stabilizing the astrocytic process will be evaluated after anti-sense oligonucleotide down regulation of GFAP levels. The Sf9 cells will be used as a model system with certain features of the nerve axon to investigate the interactions between microtubule accessory proteins and the neuronal intermediate filaments. Proteins which will be studied include HMW tau, LMW tau, various domains of the tau molecule, MAP1b and its light chain, peripherin, NF-L, NF-M and NF-H.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015076-22
Application #
6186960
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Murphy, Diane
Project Start
1989-06-01
Project End
2002-05-31
Budget Start
2000-06-01
Budget End
2002-05-31
Support Year
22
Fiscal Year
2000
Total Cost
$347,558
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Padmanabhan, Jaya; Brown, Kristy R; Padilla, Amelia et al. (2015) Functional role of RNA polymerase II and P70 S6 kinase in KCl withdrawal-induced cerebellar granule neuron apoptosis. J Biol Chem 290:5267-79
Pozueta, Julio; Lefort, Roger; Ribe, Elena M et al. (2013) Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice. Nat Commun 4:1939
Gong, Bing; Chen, Fei; Pan, Yong et al. (2010) SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer's disease amyloidosis and improves synaptic function. Aging Cell 9:1018-31
Vitolo, Ottavio; Gong, Bing; Cao, Zixuan et al. (2009) Protection against beta-amyloid induced abnormal synaptic function and cell death by Ginkgolide J. Neurobiol Aging 30:257-65
Smith, Donna L; Pozueta, Julio; Gong, Bing et al. (2009) Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proc Natl Acad Sci U S A 106:16877-82
Lopez-Toledano, Miguel A; Shelanski, Michael L (2007) Increased neurogenesis in young transgenic mice overexpressing human APP(Sw, Ind). J Alzheimers Dis 12:229-40
Padmanabhan, Jaya; Brown, Kristy; Shelanski, Michael L (2007) Cell cycle inhibition and retinoblastoma protein overexpression prevent Purkinje cell death in organotypic slice cultures. Dev Neurobiol 67:818-26
Shrestha, Brikha R; Vitolo, Ottavio V; Joshi, Powrnima et al. (2006) Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons. Mol Cell Neurosci 33:274-82
Gong, Bing; Cao, Zixuan; Zheng, Ping et al. (2006) Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell 126:775-88
Puzzo, Daniela; Vitolo, Ottavio; Trinchese, Fabrizio et al. (2005) Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity. J Neurosci 25:6887-97

Showing the most recent 10 out of 32 publications