Content:
This thesis addresses the role of a Schwann cell laminin-receptor, dystroglycan, in the regulation of both nodal and internodal architecture, to provide the nerve with the proper structure that is ultimately needed to accomplish its electrical function. By pairing with different dystrophin-like proteins (utrophin, Dp116 and DRP2), cytoskeletal and cytoskeletal-adaptor proteins (actin) and extracellular-matrix ligands (laminins, agrin and perlecan), dystroglycan forms complexes that are differently localized throughout the nerve and that may have specific functions in radial sorting, compartmentalization of the myelinated fiber and organization of nodes of Ranvier. In the present thesis I will focus on the role of Schwann cell dystroglycan in nodal architecture (1), and I will analyze how DG cleavage by matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) can regulate Schwann cell cytoplasm compartmentalization and internodal lenght in both physiological and pathological conditions (2). These two sub-projects have the following specific objectives: 1. To understand if the defect in Nav clustering at nodes of Ranvier in the absence of dystroglycan is developmentally-determined or acquired with age; to unravel the mechanism/s through which Schwann cell dystroglycan aids Nav clustering (Chapter 2). 2. To understand if post-translational modification of dystroglycan by metalloproteainases 2 and 9 can alter the compartmentalization of Schwann cell cytoplasm and how this influence the Schwann cell phenotype in physiological conditions; to evaluate if the ablation of MMP9, which is elevated in nerves of dystrophic mice (model of MDC1A), could ameliorate the peripheral neuropathy (Chapter 3).
Note:
Dissertation Università degli Studi di Milano-Bicocca 2012
Language:
English
