The overall goal of these studies is to define the role that gap junctions play in the functions of myelinating, non-myelinating and proliferating Schwann cells in the peripheral nervous system. Because point mutations in Cx32 are responsible for the X-linked form of Charcot-Marie-Tooth syndrome (CMTX), a demyelinating peripheral neuropathy, we are particularly interested in correlated changes in Cx32 expression with myelination in vivo and in culture and in properties of CMTX mutant channels. Because expression of other gap junction proteins (connexins) can be induced in myelinating Schwann cells by nerve injury, we are also interested in the nature of this induction and the changes in Schwann cell behavior when different connexin are expressed. We will apply a broadly based approach to the studies, taking advantage of recently developed animal models deficient in myelin proteins and making use of transfection technology in Schwann cells and cell lines.
Specific Aim 1. To compare the functional properties of Schwann cells cultured from myelinated and nonmyelinated nerves of wildtype mice and transgenic mice in which connexin expression is altered.
Specific Aim 2. To determine turnover dynamics and transport characteristics of the connexins and their mRNAs that are expressed in myelinating, nonmyelinating and proliferating Schwann cells in wildtype and connexin-altered transgenic mice.
Specific Aim 3. To determine the impact of myelin-related genes on gap junction properties using transfected cell lines and Schwann cells cultured from transgenic mice in which myelin-related proteins are altered. Together, these studies should answer major questions regarding basic biology of Schwann cells and the role of gap junctions in physiological and pathophysiological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034931-07
Application #
6539858
Study Section
Special Emphasis Panel (ZRG1-MDCN-3 (01))
Program Officer
Nichols, Paul L
Project Start
1996-02-05
Project End
2003-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
7
Fiscal Year
2002
Total Cost
$326,516
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Bai, Donglin; del Corsso, Cristiane; Srinivas, Miduturu et al. (2006) Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB). J Pharmacol Exp Ther 319:1452-8
Thi, Mia M; Kojima, Takashi; Cowin, Stephen C et al. (2003) Fluid shear stress remodels expression and function of junctional proteins in cultured bone cells. Am J Physiol Cell Physiol 284:C389-403
Duffy, Heather S; O'Donnell, Phyllis; Coombs, Wanda et al. (2003) Kinetics of protein-protein interactions of connexins: use of enzyme linked sorbent assays. Cell Commun Adhes 10:207-10
Iacobas, D A; Urban, Marcia; Iacobas, Sanda et al. (2002) Transcriptomic characterization of four classes of cell-cell/cell-matrix genes in brains and hearts of wild type and connexin43 null mice. Rom J Physiol 39-40:91-116
Iacobas, D A; Urban, Marcia; Iacobas, Sanda et al. (2002) Control and variability of gene expression in mouse brain and in a neuroblastoma cell line. Rom J Physiol 39-40:71-90
Zoidl, G; Meier, C; Petrasch-Parwez, E et al. (2002) Evidence for a role of the N-terminal domain in subcellular localization of the neuronal connexin36 (Cx36). J Neurosci Res 69:448-65
Rozental, R; Andrade-Rozental, A F; Zheng, X et al. (2001) Gap junction-mediated bidirectional signaling between human fetal hippocampal neurons and astrocytes. Dev Neurosci 23:420-31
De Pina-Benabou, M H; Srinivas, M; Spray, D C et al. (2001) Calmodulin kinase pathway mediates the K+-induced increase in Gap junctional communication between mouse spinal cord astrocytes. J Neurosci 21:6635-43
Duffy, H S; Delmar, M; Coombs, W et al. (2001) Functional demonstration of connexin-protein binding using surface plasmon resonance. Cell Commun Adhes 8:225-9
Srinivas, M; Hopperstad, M G; Spray, D C (2001) Quinine blocks specific gap junction channel subtypes. Proc Natl Acad Sci U S A 98:10942-7

Showing the most recent 10 out of 22 publications