Molecular and mechanical functions of the intermediate filament protein GFAP

Research output: ThesisPhd Thesis 4 Research NOT TU/e / Graduation NOT TU/e)

Abstract

All cells in the body have a cytoskeleton important for cell shape, motility, organization, and signalling processes. A hallmark protein of the cytoskeleton of astrocytes and astrocytoma cells is Glial Fibrillary Acidic Protein (GFAP). Although this protein is used as a marker of these cells, little is known of its function. In addition, multiple isoforms of the protein exist, with the canonical GFAPα and the neurogenic niche enriched GFAPδ as the most common isoforms. We studied the production of GFAP on astrocytic cell lines after mechanical injury, and surprisingly found these cells are resilient to injury. By using both in vitro and in vivo modulations of GFAP in multiple models, both in primary astrocytes, as well as in astrocytoma cell lines, we found that the different isoforms have different effects on the mechanics and the dynamics of the network as well as on cell-environment interactions. This includes changes in expression of genes encoding for proteins that are components of cell-extracellular matrix interactions, cell-cell interactions, and the signalling pathways involved in these processes. These processes are important and often deregulated in the progression of tumour malignance. Therefore further investigation into the relation between GFAP isoforms and these processes will help us understand tumour biology and will help us uncover novel therapeutic targets for cancer treatment.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam
Supervisors/Advisors
  • Hol, Elly M., Promotor, External person
  • Koenderink, Gijsje H., Promotor, External person
  • Kamphuis, Willem, Copromotor, External person
Thesis sponsors
Award date2 Dec 2016
Print ISBNs978-94-6169-981-7
Publication statusPublished - 2 Dec 2016

Bibliographical note

Research conducted at: Universiteit van Amsterdam

Keywords

  • Intermediate Filaments
  • GFAP
  • Astrocytes
  • Microarray
  • Astrocytoma
  • microrheology
  • Mechanical injury

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