Abstract

This proposal builds on observations made during the current grant period that the over-expression of the neuronal intermediate filament protein alpha-internexin causes the formation of axonal swellings in transgenic mice, as well as observations made with GFP-intermediate filament protein chimeras which suggest an interaction between intermediate filaments and the microtubule cytoskeleton. It also builds on the recent characterization of BPAG1, which has both an intermediate filament-binding domain and an actin-binding domain. The emphasis of the current proposal is to examine proteins which interact with neuronal intermediate filaments, to identify motor proteins involved in the transport of neuronal intermediate filaments, and to make further progress in understanding the function and regulation of the neuronal intermediate filament protein a-internexin.
The specific aims of this study are: (1) to study how members of the plakin family interact with neuronal intermediate filaments; (2) to study the mechanism of the transport of neuronal intermediate filaments in the axon; and (3) to continue studies on the function of alpha-internexin by generating a knockout mouse model and characterizing the resulting phenotype.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015182-22
Application #
6188233
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Chiu, Arlene Y
Project Start
1987-07-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
22
Fiscal Year
2000
Total Cost
$380,897
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

Liem, Ronald K H; Messing, Albee (2009) Dysfunctions of neuronal and glial intermediate filaments in disease. J Clin Invest 119:1814-24
Ching, Gee Y; Liem, Ronald K H (2009) RE1 silencing transcription factor is involved in regulating neuron-specific expression of alpha-internexin and neurofilament genes. J Neurochem 109:1610-23
Goryunov, Dmitry; Nightingale, Andrew; Bornfleth, Lorelei et al. (2008) Multiple disease-linked myotubularin mutations cause NFL assembly defects in cultured cells and disrupt myotubularin dimerization. J Neurochem 104:1536-52
Kabzinska, Dagmara; Perez-Olle, Raul; Goryunov, Dmitry et al. (2006) Is a novel I214M substitution in the NEFL gene a cause of Charcot-Marie-Tooth disease? Functional analysis using cell culture models. J Peripher Nerv Syst 11:225-31
Perez-Olle, Raul; Lopez-Toledano, Miguel A; Goryunov, Dmitry et al. (2005) Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease cause defects in transport. J Neurochem 93:861-74
Perez-Olle, Raul; Jones, Sidonie T; Liem, Ronald K H (2004) Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models. Hum Mol Genet 13:2207-20
Perez-Olle, Raul; Lopez-Toledano, Miguel A; Liem, Ronald K H (2004) The G336S variant in the human neurofilament-M gene does not affect its assembly or distribution: importance of the functional analysis of neurofilament variants. J Neuropathol Exp Neurol 63:759-74
Leung, Conrad L; He, Cui Zhen; Kaufmann, Petra et al. (2004) A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis. Brain Pathol 14:290-6
Leung, Conrad L; Green, Kathleen J; Liem, Ronald K H (2002) Plakins: a family of versatile cytolinker proteins. Trends Cell Biol 12:37-45
Perez-Olle, Raul; Leung, Conrad L; Liem, Ronald K H (2002) Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation. J Cell Sci 115:4937-46

Showing the most recent 10 out of 49 publications