Item – Theses Canada

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OCLC number
720806942
Link(s) to full text
LAC copy
LAC copy
Author
Huang, Kuo-Cheng,1978-
Title
The secret life of a novel cell adhesion molecule CAR the Coxsackie and Adenovirus Receptor in neuronal development.
Degree
Ph. D. -- McGill University, 2008
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2010]
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
The Coxsackie and Adenovirus Receptor (CAR) is an adhesion molecule of the immunoglobulin superfamily. CAR is expressed highly in the developing brain, but its physiological function is not known. Our 'in vivo' subcellular fractionation of developing mouse brain and immunostaining of hippocampal neurons in culture showed CAR to be enriched in growth cones. Proteomic analysis of purified growth cones revealed that CAR binds tubulin and actin. In hippocampal cultures, CAR localized to areas of F-actin and microtubule interaction in the growth cone, and its proper localization was dependent on the integrity of both cytoskeletal systems. In addition, CAR immunoprecipitated with components of the ERK1/2 MAPK signaling pathway. Since all these interactors are implicated in neurite outgrowth, we hypothesized that CAR may play a role in this process. We demonstrated that neurons plated on coverslips coated with the extracellular domain of CAR display enhanced neurite outgrowth. Furthermore, the enhanced neurite outgrowth depends on expression of endogenous CAR. We have also shown that the extracellular domain of CAR is shed to the medium by a metalloprotease-dependent mechanism, pointing to the physiological relevance of enhanced neurite outgrowth mediated by this domain. Interestingly, CAR localizes to cholesterol-sphingolipid rich microdomains in developing neurons and coimmunoprecipitates with known lipid-raft signaling proteins such as nNOS, pointing to a possible function of CAR in lipid-raft signaling. These studies indicate that CAR is not just a virus receptor but is an important regulator of developmental processes in the brain.
ISBN
9780494508299
0494508299