Dr. Hortsch proposes to continue his investigation of the mechanism by which neuroglian/L1-CAM recruits ankyrin to the vicinity of the plasma membrane in Drosophila embryos and transfected S2 cells. He proposes a number of straightforward deletion and replacement mutagenesis studies to analyze which domains of neuroglian are required to recruit ankyrin. He also will use yeast two-hybrid and ankyrin affinity chromatography approaches to identify additional ankyrin-binding membrane proteins in Drosophila and will use transgenic Drosophila lines containing myc-tagged ankyrin to demonstrate the in vivo effects of neuroglian mutants. Finally, he will use this assay system to test whether mutant L1-CAM molecules from human patients will function in his assay.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029388-07
Application #
2889061
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Henken, Deborah B
Project Start
1978-02-01
Project End
2003-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Goossens, Tim; Kang, Yuan Y; Wuytens, Gunther et al. (2011) The Drosophila L1CAM homolog Neuroglian signals through distinct pathways to control different aspects of mushroom body axon development. Development 138:1595-605
Carhan, A; Allen, F; Armstrong, J D et al. (2005) Female receptivity phenotype of icebox mutants caused by a mutation in the L1-type cell adhesion molecule neuroglian. Genes Brain Behav 4:449-65
Wei, Jun; Hortsch, Michael; Goode, Scott (2004) Neuroglian stabilizes epithelial structure during Drosophila oogenesis. Dev Dyn 230:800-8
Islam, Rafique; Kristiansen, Lars V; Romani, Susana et al. (2004) Activation of EGF receptor kinase by L1-mediated homophilic cell interactions. Mol Biol Cell 15:2003-12
Malhotra, Jyoti D; Koopmann, Matthew C; Kazen-Gillespie, Kristin A et al. (2002) Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin. J Biol Chem 277:26681-8