Susan D. Kraner: Personal Page

SUSAN KRANER, PhD

RESEARCH INTERESTS: Transcription, regulation of sodium channel gene expression, targeting and distribution of muscle sodium channels in the surface membrane, synapse formation.

RESEARCH TECHNIQUES: Molecular biology and biochemistry, immunohistochemistry, confocal microscopy, adenoviral-mediated gene transfer in vivo.

RESEARCH SUMMARY:Research in the Kraner lab focuses on two inter-related issues:

Regulation of ion channel gene and functional protein expression by a variety of transcription factors and cell signaling pathways, and
Regulation of other genes and proteins through these same ion channels.

Voltage-gated ion channels drive cellular communication in nerve, muscle and cardiac tissue. Our work focuses on voltage-gated Na⁺ channels and L-type voltage-gated Ca²⁺ channels. Na⁺ channels are responsible for propagating the regenerative action potential that is the fundamental unit of signaling in excitable cells, and Ca²⁺ channels regulate both electrical excitability and downstream processes such as changes in gene expression that underlie the processes of learning and memory. Our overall goal is to understand how changes in ion gene expression contribute to development, synapse-formation and regeneration of skeletal muscle or to age-related cognitive decline in the hippocampus.

To achieve these goals, my colleagues and I have developed sophisticated molecular tools to analyze expression of ion channels and their promoter regions. We use many standard molecular and biochemical approaches such as channel immunopurification, Western blotting, site-directed mutational analysis of promoter regions in transient transfection assays and EMSAs, and immunocytochemistry. Additionally, we have developed viral vectors to drive expression of key regulatory factors, such as calcineurin, a protein phosphatase activated by Ca²⁺-influx through L-type voltage-gated Ca²⁺ channels. We are studying the effects of these regulatory proteins in both our standard assays and, in collaboration with Drs. Chris Norris, Eric Blalock, and Phil Landfield, in gene microarrays. In addition, we are using knockout mice to study the role transcription factors play in regulating ion channel gene expression. Utilizing these tools, we aim to determine how the interplay between transcription factors, Ca²⁺-regulated factors and ion channels regulate development and age-related decline in muscle and nerve.

KEY WORDS: sodium channel, neuromuscular junction, basic helix-loop-helix transcription factors, muscle development

KEY REFERENCES

Blalock, EM. Chen, K-C. Stromberg, AJ. Norris, CM. Kadish, I. Kraner SD. Porter, NM. Landfield, PW. Harnessing the power of gene microarrays for the study of brain aging and Alzheimer's Disease: Statistical reliability and functional correlation, Aging Research Reviews, in press.

Thompson, AL. Filatov G. Chen C. Porter I. Li Y. Rich MM. and Kraner SD. A selective role for MRF4 in innervated adult skeletal muscle: NaV 1.4 Na+ channel expression is reduced in MRF4-null mice, Gene Expression, in press.

Norris, CM., Kadish, I., Blalock, EM., Chen, KC., Thibault, V. Porter, NM., Landfield, PW., Kraner, SD. Calcineurin triggers reactive/inflammatory processes in astrocytes and is upregulated in aging and Alzheimer's models, Journal Neurosci. 25: 4649-4658, 2005.

Swanson HI. Kraner SD. Ray SS. Hoagland M. Thompson ED. Zheng X. Tian Y. Experimental approaches for the study of cytochrome P450 gene regulation. In "Drug Metabolism and Transport: Molecular Methods and Mechanisms", L. Lash, Eds. Humana Press, 2004.

Kraner SD. Rich MM. Sholl MA. Zhou HY. Zorc C. Kallen RG. Barchi RL. (1999) Interaction Between the Skeletal Muscle Type 1 Na+ Channel Promoter E box and an Upstream Repressor Element. Release of Repression by Myogenin. Journal of Biological Chemistry, 274: 8129-8136.

Kraner SD. Rich MM. Kallen RG. Barchi RL. (1998) Two E-boxes are the focal point of muscle-specific skeletal muscle type 1 Na+ channel gene expression. Journal of Biological Chemistry, 273: 11327-34.

Kraner SD. Filatov GN. Sun W. Bannerman P. Lindstrom J. Barchi RL. (1998) Analysis of local structure in the D2/S1-S2 region of the rat skeletal muscle type 1 sodium channel using insertional mutagenesis. Journal of Neurochemistry, 70: 1628-35.

Chong JA. Tapia-Ramirez J. Kim S. Toledo-Aral JJ. Zheng Y. Boutros MC. Altshuller YM. Frohman MA. Kraner SD. Mandel G. (1995) REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell, 80: 949-57.

Kraner SD. Chong JA. Tsay HJ. Mandel G. (1992) Silencing the type II sodium channel gene: a model for neural-specific gene regulation. Neuron, 9: 37-44.