TMEM67 is required for the maintenance of the perinuclear actin cap
Toynbee, A
Date: 10 June 2019
Thesis or dissertation
Publisher
University of Exeter
Degree Title
Masters by Research in Biological Sciences
Abstract
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous disease characterised by the phenotypic triad of occipital encephalocele, polycystic kidneys, and polydactyly. MKS is classified as a ciliopathy as mutations to the MKS proteins result in dysfunction to the primary cilium. Recent research has expanded the aetiology of MKS, as ...
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous disease characterised by the phenotypic triad of occipital encephalocele, polycystic kidneys, and polydactyly. MKS is classified as a ciliopathy as mutations to the MKS proteins result in dysfunction to the primary cilium. Recent research has expanded the aetiology of MKS, as increasing evidence for non-ciliary roles for the MKS proteins are uncovered. Evidence includes their presence at focal adhesions and a role in controlling extracellular matrix (ECM) morphology. The relative contributions of ciliary and non-ciliary cellular phenotypes to the clinical presentations of MKS are not currently known. This thesis identifies ECM-dependent aberrations to the perinuclear actin cap in MKS patient cells lacking the MKS type 3 transmembrane protein TMEM67, likely contributing to migration defects previously identified in patient cells. Furthermore, GFP-Trap analysis identifies a number of myosins as potential binding partners of TMEM67; a previously unreported association. Analysis of these binding partners reports the top biological processes for TMEM67 as myosin-motor activity and actin-based movement, adding to the potential non-ciliary roles of the protein already reported. By expanding our understanding of the role of ciliopathy proteins outside of the cilium, we better comprehend the aetiology of the diseases, providing an opportunity to find new therapeutic interventions.
MbyRes Dissertations
Doctoral College
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