Learning how axons of retinal ganglion cells grow from their origins in the retina to their targets in the brain is an important goal for understanding how the visual system develops. A number of cell adhesion molecules (CAMs) have been found in the optic fiber layer and optic nerve and are thought to be important in axon growth and guidance. We have found that one CAM, called L1 (also referred to as NILE, Ng-CAM, 8D9 or G4), is present on axon of retinal ganglion cells and is a potent substrate for growth of axons of retinal ganglion cells in vitro. Moreover, preliminary experiments suggest that L1 may be able to support axon regeneration in the adult nervous system. The experiments described in this proposal will provide important new information about how L1 participates in visual system development and will extend our knowledge about how CAMs can function to promote and guide axon growth following damage to the visual system. Biochemical, immunological and molecular biological experiments will examine how L1 binding functions in axon adhesion. In vitro experiments will investigate how L1 mediated axonal adhesion functions in guiding axons along visual pathways. In vivo experiments will evaluate the ability of purified L1 to promote axon growth in the visual system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005285-12
Application #
3260279
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1988-09-01
Project End
1994-06-30
Budget Start
1992-12-01
Budget End
1994-06-30
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Gavert, Nancy; Ben-Shmuel, Amir; Lemmon, Vance et al. (2010) Nuclear factor-kappaB signaling and ezrin are essential for L1-mediated metastasis of colon cancer cells. J Cell Sci 123:2135-43
Tapanes-Castillo, Alexis; Weaver, Eli J; Smith, Robin P et al. (2010) A modifier locus on chromosome 5 contributes to L1 cell adhesion molecule X-linked hydrocephalus in mice. Neurogenetics 11:53-71
Tyukhtenko, Sergiy; Deshmukh, Lalit; Kumar, Vineet et al. (2008) Characterization of the neuron-specific L1-CAM cytoplasmic tail: naturally disordered in solution it exercises different binding modes for different adaptor proteins. Biochemistry 47:4160-8
Bechara, Ahmad; Nawabi, Homaira; Moret, Frederic et al. (2008) FAK-MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse. EMBO J 27:1549-62
Buchser, William J; Pardinas, Jose R; Shi, Yan et al. (2006) 96-well electroporation method for transfection of mammalian central neurons. Biotechniques 41:619-24
Cheng, Ling; Lemmon, Sandra; Lemmon, Vance (2005) RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated protein kinase activation. J Neurochem 94:1102-10
Newpher, Thomas M; Smith, Robin P; Lemmon, Vance et al. (2005) In vivo dynamics of clathrin and its adaptor-dependent recruitment to the actin-based endocytic machinery in yeast. Dev Cell 9:87-98
Cheng, Ling; Itoh, Kouichi; Lemmon, Vance (2005) L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region. J Neurosci 25:395-403
Itoh, Kyoko; Fushiki, Shinji; Kamiguchi, Hiroyuki et al. (2005) Disrupted Schwann cell-axon interactions in peripheral nerves of mice with altered L1-integrin interactions. Mol Cell Neurosci 30:131-6
Itoh, Kouichi; Shimono, Ken; Lemmon, Vance (2005) Dephosphorylation and internalization of cell adhesion molecule L1 induced by theta burst stimulation in rat hippocampus. Mol Cell Neurosci 29:245-9

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